1. Blood cells

2. Blood Blood makes up about 7% of a body’s weight
An average adult has pints of blood
Four main blood types: A, O, B, AB
Rh positive or negative
Universal Donor: O-
Universal Recipient: AB +

3. Complete Blood Count
CBC or Hemogram: one of the most commonly ordered lab tests. It assesses:
White blood cells (WBC)
Red blood cells (RBC)
Platelets (PLT)
WBC Differential

4. The Complete Blood Cell Count
TABLE 1 The Complete Blood Cell Count
Parameter
Normal adult range
Indications
Hemoglobin
Male: 14.0 – 17.4 mg/dL Female: 12.0 – 16.0 mg/dL
Low: Anemia High: Polycythemia
Hematocrit
Male: 42% – 52% Female: 35% – 48%
RBC count
Male: 4.5 – 5.5 x 106/µL Female: 4.0 – 5.0 x 106/µL
WBC count
5.0 – 10.0 x 103/µL
Low: Leukopenia High: Leukocytosis
Platelet count
140 – 400 x 103/µL
Low: Thrombocytopenia High: Thrombocytosis
Reticulocyte count
0.5% – 1.5% 25 – 85 x 103/µL
Low in anemia: Low marrow output High: RBC loss
RBC, red blood cell; WBC, white blood cell.
Data extracted from: Fischbach FT. A Manual of Laboratory and Diagnostic Tests. Philadelphia, Pa: Lippincott Williams & Wilkins; 2003:47.

5. White blood cells
WBC Count: "Never Let Mom Eat Beans" and "60, 30, 6, 3, 1"
Neutrophils 60%
Lymphocytes 30%
Monocytes 6%
Eosinophils 3%
Basophils 1:

6. WBC Differential: Types of Cells
Neutrophils (infection-fighters)
segs or polys (mature)
bands or stabs (young)
Lymphocytes (immunity)
Monocytes (phagocytosis)
Eosinophils (allergy, parasites)
Basophils (hypersensitivity)
Blasts (very immature)
(Blasts should ALWAYS be considered ABNORMAL unless proven otherwise)

7. Red Blood Cells
Red blood cells transport oxygen from the lungs to the organs and peripheral tissues, then return to the lungs carrying carbon dioxide to be exhaled. RBCs are pliable and designed to traverse the small capillary beds. RBCs contain the oxygen carrying protein Hemoglobin (HGB). Hematocrit measures the % of RBC mass in 100ml blood.
Normal RBC life span = 120 days

8. Red Blood Cells Reticulocytes: immature RBCs
Number helps to determine causes of anemia. Normal retic count is %
Low retic <1%= decreased marrow production of RBCs causing anemia
Elevated Retic > 2% = indicates anemia caused by RBC loss

9. RBC RBC count Hemoglobin Hematocrit
total # of RBCs in each cc of blood
Hemoglobin
iron-rich protein found inside RBCs, measured in gm/dl
indicator of O2-carrying capacity
Hematocrit
% of RBC’s by volume

10. Red Blood Cell Assessment: Size & Color
MCV (mean cell volume)
RBC size
MCH (mean cell hemoglobin)
MCHC (mean cell hemoglobin concentration)
RBC hemoglobin content (color)
RDW (red cell distribution width)
Variation in RBC size

11. The RBC indices are useful for assessing the size and color of the red blood cells:
MCV (mean cell volume) indicates red cell size
MCH (mean cell hemoglobin) indicates amount of hemoglobin in each RBC
MCHC (mean cell hemoglobin concentration) indicates the concentration of hemoglobin per RBC (related to the hydration status of the RBC)
MCH and MCHC are both indicative of RBC color (pale vs. normal)
RDW (red cell distribution width) indicates variations in the size of RBCs

12. Normal RBC

13. The production of RBC’s is called ????????
RBC production is regulated by the tissues demand for o2. A lack of o2 stimulates the formation and release of erythropoietin. This hormone activates bone marrow to produce RBC’s.
80-90% of erythropoietin is made in the kidneys and the rest in the liver.

14. Erythrocytes begin with stem cells. These eventually develop into RBC’s. But the development requires vitamin B12, folic acid, and minerals(especially??)

15. Anemia of Decreased Marrow Production
When the marrow slows production due to insufficient erythropoietin (EPO), lack of other vital elements in RBC production including iron, folate, B12, or attack on the bone marrow by a virus, toxin or cancer.
Causes of this type of anemia are many, but most commonly we see it in patients with kidney problems, or arthritis, such as rheumatoid arthritis, or lupus.  Also, in patients with cancer and certain blood disorders, such as myelodysplasia.
The mean corpuscular volume (MCV) is the most useful parameter to evaluate a low retic count anemia

16. Anemia of Decreased Marrow Production
Treatment is Erythropoetin, given periodically in the form of a subcutaneous injection.  Erythropoetin is a hormone, normally secreted in the kidneys of healthy persons.  Before one considers treatment with Erythropoetin, it is important that other causes of anemia have been ruled out, or erythropoietin will not work.

17. MICROCYTIC ANEMIAS

18. Microcytic Anemias have low MCV (< 80)
most common type of anemia encountered in primary care
Differential diagnosis: Iron deficiency anemia, thalassemia, anemia of chronic disease/inflammation, sideroblastic anemia

19. Microcytic Anemia TABLE 3 Laboratory Findings in Microcytic Anemias
Red cell morphology
Serum iron level
Total iron-binding capacity
Percent saturation
Serum ferritin level
Iron deficiency anemia
Microcytic, hypochromic
Decreased
Increased
< 16%
Anemia of chronic inflammation
Normocytic, microcytic
10% – 20%
Sideroblastic anemia
Normal
50% – 100%
Thalassemia
Microcytic, target cells
Normal or increased
30% – 100%
Data extracted from: Massey. Med Clin North Am ; Adamson JW. Iron deficiency and other hypoproliferative anemias. In: Kasper DL, Braunwald E, Fauci A, et al, eds. Harrison’s Principles of Internal Medicine. 16th ed. New York, NY: McGraw-Hill Professional; 2004:

20. Iron deficiency anemia
Hypochromic

21. Iron Deficiency Anemia
Definition: anemia occurs when body iron stores are depleted by prolonged bleeding without replacement. Other causes can include inadequate iron stores due to poor dietary intake and or poor absorption or utilization
Incidence: common, seen in up to 20% of women, 50% of pregnant women and 3% of men
Lab findings: anemia, low retic, low MCV and low MCHC, low ferritin, low % iron saturation, elevated TIBC, possible thrombocytosis
Signs and Symptoms: fatigue, pallor, pica, blood loss
Exam findings: pallor, pale conjunctiva, koilonychia, angular stomatitis, glossitis. More severe anemia may see tachycardia, tachypnea

22. Iron deficiency anemia
We must first must identify etiology in order to plan management
GI bleeding
Menorrhagia
Pregnancy
Poor intake
Lack of absorption

24. Iron deficiency anemia
Repletion of iron
Oral Iron
Ferrous Sulfate 320mg bid-tid (most common, GI side effects)
Ferrous Gluconate 325 mg bid-tid(better tolerated)
Niferex 150 mg qd
Repliva 1 po qd (taken 21 of 28 days)
Vitamin C aids absorption of iron. Milk/calcium products hamper absorption
* Will need 3-6 months of oral iron to replete stores. If no response, or unable to tolerate or absorb, refer to hematology for intravenous iron therapy (Infed, Ferrlicit, Venofur)

25. My sad story 
Affairs/press_releases/press08/LaurelOncologistPleads GuiltytoPurchasingMisbrandedDrugs.html

26. Sideroblastic Anemia
Definition: anemia characterized by ringed-sideroblasts. Caused by an enzyme disorder in which the body has adequate iron but is unable to incorporate it into hemoglobin. Iron enters the developing red blood cell where iron accumulates in the mitochondria giving a ringed appearance to the nucleus (ie: ringed sideroblast). Can be caused by genetic defect, toxin exposure or idiopathic.
Lab findings: microcytic anemia, basophilic stippling on peripheral smear, usually normal iron studies. Bone marrow biopsy needed if this anemia is suspected based on presentation and peripheral smear. Check blood ETOH, lead levels

27. Sideroblastic anemia

28. Sideroblastic anemia
Signs and Symptoms: depend on cause. May have history of ETOH abuse, have altered mental status, abdominal pain or neuropathy, history of treatment for TB, fatigue, pallor, family history
Physical findings: pallor, abnormal neuro exam with decreased sensory perception, tender abdomen, evidence of ETOH, enlarged spleen or liver, cardiac arrhythmia
Management: refer to hematology for management. Sometimes treated as a Myelodysplastic syndrome with epo growth factors. May progress to aplastic anemia requiring bone marrow transplant

29. Hemolytic Anemias

30. Hemolytic anemias
Hemolytic anemia – occurs when the bone marrow is unable to make up for premature destruction of red blood cells by increasing their production. Hemolysis can be triggered by infection, medications, auto-immune responses, inherited disorders (hemoglobinopathies)
There are many types of hemolytic anemia. The condition can be inherited or acquired. "Inherited" means your parents passed the gene for the condition on to you. "Acquired" means you aren't born with the condition, but you develop it.
Treatment depends on cause
Folate (folic acid) is used in all hemolytic anemias to help stabilize the RBC membrane and decrease destruction

31. Hemolytic Anemia Auto-immune hemolytic anemia - Cause is often unknown
Signs and Symptoms: usually very acute and serious with sudden rapid drop in Hgb leading to fatigue, weakness, SOB. Patient is usually hospitalized
Exam findings: pallor, tachycardia, tachypnea, jaundice, splenomegaly
Labs: low Hgb/Hct, + direct Coomb’s, elevated bilirubin, elevated LDH, low serum haptoglobin, elevated retic count
Diff Dx: anemia secondary to blood loss, hemoglobinopathy

32. Auto-Immune Hemolytic anemia
Treatment:
Steroids, usually Prednisone at high dose (1mg/kg) to help suppress the immune system. Gradual taper over weeks to months. Splenectomy is often considered followed by other types of immune modulation if hemolysis is not improving. Blood transfusions can be used to off set severe anemia however there is increased risk for antibody development and reactions
This can be a chronic relapsing disease

33. Thalassemia Syndromes
Definition: inherited genetic disorders that cause decreased production of normal Hgb A.
Three types:
Beta Thalassemia major
Beta Thalassemia minor
Alpha Thalassemia
Incidence: In b thalassemia can be as high as 1 in 10 in certain Mediterranean populations. In the US approx 2 million people have some form of thalassemia trait or disease. Thalassemia is the most common genetic disorder worldwide.

34. Fun Fact
A screening policy exists in Cyprus to reduce the incidence of thalassemia, which since the program's implementation in the 1970s (which also includes pre- natal screening and abortion) has reduced the number of children born with the hereditary blood disease from 1 out of every 158 births to almost zero

35. β Thalassemia Major
Most severe form. Also known as Cooley’s anemia. Anemia begins to develop within the first months after birth. It becomes progressively more and more severe. The infant fails to thrive (to grow normally) and often has problems feeding (due to easy fatigue from lack of oxygen, with the profound anemia), bouts of fever (due to infections to which the severe anemia predisposes the child) and diarrhea and other intestinal problems.
Lab findings: Hgb electropheresis would show increase in Hgb A2 and F with no normal Hgb A
Signs and symptoms usually present in infants prior to 6 months of age including irritability, poor feeding, pallor
Physical findings: severe anemia, jaundice and hepatosplenomegaly, as well as growth retardation
Management includes life long chronic blood transfusions to replace abnormal Hgb with normal Hgb. Chronic transfusions lead to iron overload which must be removed from the body with chelation therapy (Desferol, Exjade) to avoid liver and heart failure.

36. β Thalassemia Minor
Definition: less severe form of thalassemia whereby pt does produce some normal Hgb A. Persons with thalassemia minor have (at most) mild anemia (with slight lowering of the hemoglobin level in the blood). This situation can very closely resemble that with mild iron-deficiency anemia. However, persons with thalassemia minor have a normal blood iron level (unless they have are iron deficient for other reasons). No treatment is necessary for thalassemia minor. In particular, iron is neither necessary nor advised
Labs: Hgb electropheresis shows decreased Hgb A and increased Hgb A2 and F. Peripheral smear often shows target cells and basophilic stippling. Iron studies are normal
Signs and Symptoms are usually absent
Physical exam: normal or may have splenomegaly
Management: no specific therapy is required. Iron supplements are not recommended unless iron studies confirm iron deficiency with low ferritin

37.  Thalassemia
Definition: Genetic disorder of the A-globin chain. 4 loci of alpha globin and severity of disease depends on number of alpha globin chains genetically affected.
Incidence: Most common thalassemia with highest incidence in those of Southeast Asian, Mediterranean and African decent.
Labs: Microcytic RBC, with or without anemia. May have elevated RBC count. Hgb electropheresis may be normal
Signs and Symptoms: none to mild symptoms of anemia including pallor, fatigue to most severe form causing fetus with hydrops fetalis and stillbirth.

38. In this condition, the lack of alpha protein is somewhat greater
In this condition, the lack of alpha protein is somewhat greater. Patients with this condition have smaller red blood cells and a mild anemia, although many patients do not experience symptoms. However, physicians often mistake mild alpha thalassemia for iron deficiency anemia and prescribe iron supplements that have no effect on the anemia.

39.  Thalassemia
Physical findings: none to more severe form of disorder causing splenomegaly to most severe form in which all 4 alpha globin chains are affected. This is not compatible with life
Management: most often there is no specific therapy. Genetic counseling recommended for families with history of thalassemias prior to pregnancy

40. Sickle cell anemia
Sickle cell anemia – genetic disorder whereby red blood cells in a stressful environment become abnormally shaped like a sickle and cause hemolysis, anemia and veno- occlusion. This leads to end-organ damage in the spleen, kidneys and liver.
Incidence: More than 70,000 Americans have sickle cell disease. About 2 million Americans, 1 in 12 African Americans - have sickle cell trait
Ethnic groups with sickle cell anemia are usually African descendants although those of Mediterranean decent can also be affected.
Labs: CBC shows anemia, adult sickle cell anemia patients usually have elevated WBC and platelet count, elevated retic, elevated bilirubin, Hgb electropheresis shows abnormal Hgb SS (more severe disease) or Hgb SC or S-beta thalassemia

41. Sickle cell anemia
Signs and symptoms: anemia occurs as abnormal RBC have a shortened life span of only about 15 days compared to the usual 120 days. The RBCs are also fragile and lack flexibility leading to veno-occlusion and resulting pain crises, as well as risk for CVA and priapism. Sickle cell veno-occlusive crises can be triggered by infection, dehydration, temperature changes and other stressors to the body.
Exam findings: scleral icteris, jaundice, splenomegaly in children (adults usually have either required splenectomy in childhood or have infarcted the spleen causing loss of spleneic function by adult age).

42. Sickle cell disease
Normal adult spleen is 11cm in craniocaudal length.
This picture illustrates a spleen that has infarcted due to sickle cell disease and shrunk to 4.5cm in length. This spleen would not be functional.

43. Sickled red blood cells

44. Pathophysiology of sickle cell disease

45. Sickle cell anemia Diff Dx: other hemoglobinopathies
Treatment: no cure for sickle cell disease other than allogeneic bone marrow transplant which carries significant risk for morbidity and mortality. Management of this chronic disease includes avoidance of known triggers of veno-occlusive crisis, daily folic acid. Analgesics for painful crisis – patients are often hospitalized for pain crisis for IV narcotic analgesics, hydration with D5W (need free water), anti-inflammatories.

46. Sickle cell disease
Hydrea is sometimes used to treat sickle cell disease and decrease frequency of pain crises and hospitalizations in adult sickle cell patients. Thought to work by increasing fetal hgb and decreasing tendency for RBC to sickle.
Vaccination with pneumococcal vaccine q5 years in adults is recommended since spleneic function is impaired.
Blood transfusions with exchange transfusion is used in serious cases of acute chest syndrome or priapism and are also used in children with sickle cell disease as prophylaxis to reduce risk of CVA.

48. G6PD deficiency
Glucose-6-phosphate dehydrogenase deficiency – a hereditary enzyme deficiency that leads to hemolysis when certain drugs are ingested that induce oxidant stress on RBCs.
Antimalarial drugs that can cause acute hemolysis in people with G6PD deficiency include primaquine, pamaquine, and chloroquine. There is evidence that other antimalarials may also exacerbate G6PD deficiency, but only at higher doses. Sulfonamides, thiazolesulfone, methylene blue, and naphthalene should also be avoided by people with G6PD deficiency, as should certain analgesics (such as aspirin, phenazopyridine, and acetanilide) and a few non-sulfa antibiotics (nalidixic acid, nitrofurantoin, isoniazid, dapsone, and furazolidone). Henna has been known to cause hemolytic crisis in G6PD-deficient infants.

49. G6PD deficiency
Incidence - Most common human enzyme deficiency affecting 400 million people worldwide. X- linked recessive disorder with more males affected than females. Occurs more often in blacks
Signs and symptoms: none unless hemolysis occurs causing anemia with fatigue, SOB, dark urine
Exam findings: none specific unless having active hemolysis
Drugs to be avoided with G6PD def:
Elitec (rasburicase), Methylene blue, Pyridium, Sulfacetamide, Sulfasalazine, Isobutyl nitrite, Nitrofuratoin, Primaquine, Sulfamethoxazole (Bactrim), Toluidine blue
*G6PD deficient patient are also allergic to fava beans

50. G6PD deficiency Labs: show evidence of hemolysis
Elevated bilirubin levels
Elevated serum LDH
Low serum haptoglobin
Hemoglobinuria
Elevated retic count
Low RBC count and hemoglobin
Heinz bodies present on examination of the peripheral blood smear using special stains
Methylene blue test
Methemoglobin reduction test – used for diagnosis

51. Fun Fact
African, Middle Eastern and South Asian people are affected the most along with those who are mixed with any of the above. A side effect of this disease is that it confers protection against malaria, in particular the form of malaria caused by Plasmodium falciparum, the most deadly form of malaria. A similar relationship exists between malaria and sickle cell disease. One theory to explain this, is that cells infected with the Plasmodium parasite are cleared more rapidly by the spleen. This phenomenon might give G6PDH deficiency carriers an evolutionary advantage by increasing their fitness in malarial endemic environments.

52. Anemia of Chronic Disease
Definition: anemia caused by inflammatory processes occurring due to long-standing infection, neoplastic disease and other inflammatory disorders including rheumatoid arthritis, SLE. These processes block iron transportation from storage sites to the bone marrow factory. Can also be associated with renal failure and decreased erythropoietin production
Incidence: second most common anemia behind iron deficiency anemia
Lab findings: CBC showing anemia, low or normal MCV, normal iron studies or low % iron saturation with normal to low TIBC, elevated CRP or sed rate, elevated BUN/creatinine. Normocytic anemia

53. Anemia of Chronic Disease
Signs and Symptoms: fatigue, pallor or asymptomatic if patient has long standing history of RA, SLE, other inflammatory disease, chronic renal failure
Physical findings: none specific
Management: Treat underlying disease
If unable to determine causative factor, refer to hematology for bone marrow biopsy

54. Macrocytic Anemia

55. Macrocytic Anemias
Definition: macrocytosis or megaloblastic anemia is characterized by anemia with elevated MCV
Incidence: fairly common, seen more in the elderly and those with history of GI pathology or surgeries
Differential Dx:B12 deficiency, folate deficiency, history of GI disorder or surgery, chemotherapy, chronic alcoholism, hypothyroidism, liver disease (hepatitis), splenectomy (loss of filtration through spleen leads to larger RBCs)

56. B12 deficiency anemia
Definition: anemia caused by inadequate B12. Can be due to inadequate dietary intake in vegans or more commonly as a result of loss of intrinsic factor which leads to inability to absorb B12 (pernicious anemia)
Lab findings: anemia on CBC, MCV elevated usually > 95. Normal or low serum B12 with elevated methylmalonic acid, normal or elevated homocysteine, anti-intrinsic factor antibodies

57. B12 deficiency
Signs and Symptoms: fatigue, pallor, neuropathy, dizziness, hair loss, memory loss/dementia in elderly, history including chronic gastritis, bariatric surgery, auto-immune disorder.
Physical findings: pallor, tachycardia, abnormal sensory neuro exam, tachypnea
Management: Cyanocobalamin 1000mcg IM weekly x 4 then monthly usually for life
B12 is poorly absorbed by the oral route

58. Folate Deficiency anemia
Definition: macrocytic anemia caused by lack of folic acid. Common in alcoholics
Lab findings: CBC with anemia, macrocytic with MCV > 95. Elevated homocysteine with low or normal serum folate
Signs and Symptoms: fatigue, pallor, unusual diet (no uncooked fruits and vegetables), alcoholism
Physical exam: none specific
Management: Folic Acid 1mg po qd
Repeat homocysteine in 3 months and if remains elevated, may increase folic acid to 2mg daily. Treatment usually long term.

59. Increased marrow production
Elevated blood cells due to over production in the marrow. Can see overproduction of RBC, WBC, Platelets

60. Erythrocytosis
Definition: Over production of red blood cells in the bone marrow.
Possible causes are:
Polycythemia Vera (PV)– myeloproliferative disorder which leads to over production of red blood cells (possibly also in WBC and Platelets) in the bone marrow.
Incidence in the US: PV is relatively rare, occurring in persons per million. Occurs more in men.
Work up should be triggered for Hgb > 15 in women and > 17 in men

61. Polycythemia

62. Polycythemia Vera
Lab tests would include RBC mass, serum erythropoietin levels (usually decreased), ABG, bone marrow biopsy usually performed, JAK 2 mutation analysis (JAK genes play important role in hematopoesis)
History and Exam findings: splenomegaly, red complexion (plethora), fatigue, headache, dizziness, assess for clotting
Diff Dx: elevated RBC from smoking, chronic cardiac or lung disease, high altitude, dehydration
Treatment – therapeutic phlebotomy 500ml weekly until Hct < 45%, then usually maintenance phlebotomy every 1-3 months. May require replacement IV fluids to avoid hypotension

63. Secondary Erythrocytosis
Definition: elevated RBC count without other blood cell abnormality. Most common causes are smoking, dehydration and environment of chronic hypoxia
Lab findings: Elevated RBC with otherwise normal WBC, platelet count. Bone marrow biopsy would show normal erythrocyte precursors, normal epo level
Diagnosis is often one of exclusion if polycythemia is ruled out
Signs and symptoms depending on cause. May have symptoms of chronic hypoxia, SOB, oxygen requirement, current tobacco use. High altitude living
Management: treat underlying cause

65. STOP HERE…move to concept map

66. Thrombocytosis Definition: elevated platelet count > 500,000
Diff Dx includes: bone marrow myeloproliferative disorder as in essential thrombocythemia (ET) or secondary to iron deficiency, splenectomy, infection, malignancy or inflammatory disease
Incidence: little data
Lab findings: CBC showing elevated platelet count. Iron studies may show iron deficiency. JAK 2 mutation analysis can be helpful
Signs and Symptoms: often asymptomatic and found on routine CBC. ET patient may experience headaches, TIAs

67. Thrombocytosis
Physical findings: eval for evidence of infection, lymphadenopathy, bleeding, thrombosis
Bone marrow needed to evaluate for ET
Usually referred to hematology for work up
Management: treat underlying cause as applicable
For ET: usually no treatment unless patient is symptomatic with headaches, TIAs, thrombosis. Treatment usually consists of Anagrelide and or Hydroxyurea. May consider at least ASA for asymptomatic patient with platelet count > 1 million.

68. Platelets

69. Thrombocytopenia Definition: platelet count < 100,000.
Differential Dx: bone marrow dysfunction, malignancy, auto- immune response, medication, chemotherapy, acute bleeding, acute thrombosis, DIC, HIT, lab error
Incidence: ITP: 100 cases per million people per year with children accounting for half of those. Females more likely to be affected.
Lab/diagnostic studies: check CBC for other cytopenias, HIT assay, platelet aggregation studies, anti-platelet antibodies, bleeding time, bone marrow biopsy would show elevated megakaryocytes (platelet precursors) in destruction problem however low megakaryocytes in bone marrow production disorder. Check DIC panel. Check cultures of blood, CSF if evidence of infection. Radiographic studies for evidence of DVT/PE. Spleneic ultrasound to eval for sequestration

70. Thrombocytopenia
Signs and symptoms: bruising, bleeding, infectious symptoms, abd pain, fever, recent history of heparin, medication use including recent chemo, thiazides, ethanol, estrogen, sulfonamides, quinine, quinidine, methyldopa, anti-epileptics
Physical findings: ecchymoses, bleeding, splenomegaly with LUQ pain, SOB, hemoptysis (with PE), unilateral lower ext edema, + homan’s sign (with DVT), erythema, swelling or other evidence of infection, petechiae
Management: depending on cause
For ITP (idiopathic thrombocytopenia purpura) need to suppress immune system since this is an auto-immune response. Usually treat with Prednisone 1mg/kg qd until platelet count back to normal range then slowly taper. Often have relapse. Can also use IVIG, Monoclonal ab therapy with Rituxan. N-Plate

71. Thrombocytopenia
For HIT (heparin induced thrombocytopenia) must discontinue all Heparin use (considered Heparin allergic). This response causes patient to be hypercoagulable despite low platelet count so patient must be anti-coagulated with Refludan/Argatroban in hospital setting and then Warfarin as out patient for 3-6 months under care of hematologist
For medication related drop – discontinue offending medication and platelets should recover rapidly. May be an expected drop post chemotherapy if being treated for cancer
For consumption from acute thrombosis, patient needs to be anti-coagulated and platelets should recover

72. Thrombocytopenia
Lab Error: can have platelet clumping due to EDTA tube this may cause platelet count to appear falsely low – peripheral smear examination can confirm normal platelet count. Blood can be collected in NA citrate tube and re-run to confirm normal count
For TTP (thrombotic thrombocytopenia purpura) this rare disorder of the anticoagulation system will cause patient to require plasmapheresis to remove inhibitors of VW factor. Give pt FFP (fresh frozen plasma) to replace normal VW factor. This is a rare but serious disease that requires care under hematologist. May see RBC schistocytes on smear

73. Bleeding Disorders Hemophilia
Definition: genetic disorder characterized by lack of blood clotting factors.
Hemophilia A: lack of factor VIII (most common). Sex linked occurring in 1:10,000 males
Hemophilia B: lack of factor IX (Christmas factor) occurring in 1:100,000 males
Labs/diagnostic testing: diagnosed by checking factor activity levels, CBC, PT/PTT, bleeding time
Signs and symptoms: easy bruising, prolonged bleeding, painful joints due to hemarthrosis. Older hemophiliacs likely to be infected with HIV due to receiving contaminated factor products

74. Hemophilia
Physical findings: Ecchymoses, bleeding, edematous painful joints
Management:
Patients with hemophilia require replacement of factor when bleeding occurs or sometimes daily based on severity of disease.

75. Bleeding Disorders Von Willebrand disease (VWD)
Definition: bleeding disorder caused by lack of Von Willebrand factor which interferes with platelet function thereby increasing risk for bleeding. Most forms of VWD are mild
Incidence: most common blood clotting disorder occurring in 1 in people
Labs: normal CBC, bleeding time (prolonged), Von Willebrand factor assay (reduced), platelet aggregation study (reduced), Ristocetin co-factor (reduced)

76. Von Willebrand Disease
Signs and symptoms: easy bruising, prolonged bleeding after surgery, dental procedure, menorrhagia, epistaxis
Physical findings: may be normal or may see ecchymoses, petechiae, bleeding
Management:
Desmopressin (DDAVP) nasal spray – helps to increase factor VIII and VW factor in the blood
Fresh frozen plasma/cryoprecipitate in acute bleeding or surgery

77. White blood cells
Definition: blood cells that fight infection. Produced in the bone marrow.
Elevated = leukocytosis
Decreased = leukopenia.

78. Leukopenia Definition: total WBC < 4,300
Differential Dx: Infection including bacterial or viral, chemotherapy, other medications (anti-epileptics, penicillins, sulfonamides, cephalosporins, thiazides, cimetidine, ethanol, immunosuppressants), hematologic malignancy, aplastic anemia, hypersplenism, auto-immune disorders, Felty’s syndrome. Low WBC can be normal in certain populations
Lab studies/diagnostic testing: CBC, differential, CMP, bone marrow biopsy

79. Leukopenia
Signs and Symptoms: maybe none, symptoms of infection, fever, lymphadenopathy, weight loss, night sweats. Check medications
Physical findings: lymphadenopathy, splenomegaly, may be asymptomatic
Management: determine underlying cause
Blacks can have asymptomatic leukopenia as baseline

80. Leukocytosis Definition: WBC > 10,800
Differential Dx: Infection, Chronic inflammation, Medications (steroids), Recovery post chemotherapy, WBC growth factors (Neupogen, Leukine, Neulasta) used in cancer therapies, hematologic malignancy (leukemia) or bone marrow dysfunction
Lab/diagnostic tests: CBC with diff, UA/cx if urinary symptoms, CXR if resp symptoms, blood cultures, LAP (leukocyte alkaline phosphotase – elevated in leukomoid reaction, decreased in leukemias)

81. Leukocytosis
Signs and Symptoms: may be asymptomatic, fever, infectious symptoms, cough, SOB, dysuria, skin infection/abcess, rash, weight loss, fatigue, night sweats
Physical findings: may be none. Erythema, edema, skin rash, lymphadenopathy, cachexia, hepatosplenomegaly, abnormal heart sounds, adventitious lung sounds
Management: determine underlying cause.
If unable to determine cause or if leukocytosis persists or is rising after treating for infection, hematology consult for bone marrow biopsy

82. Leukemia
Definition: hematologic malignancy of the bone marrow whereby abnormal immature cells crowd out normal cells. WBC can be elevated or decreased in leukemia. RBC and platelets can be normal or decreased
Types of leukemia: most common
Acute Myelogenous Leukemia
Acute Lymphocytic Leukemia
Chronic Myelogenous Leukemia
Chronic Lymphocytic Leukemia

83. Acute Leukemia
Incidence: about 7000 cases per year in US. 80% are AML, 20% ALL
Etiology is unknown for the most part. Risk factors include exposure to benzene, radiation exposure and prior treatment with cytotoxic chemotherapy
Lab findings: CBC can show elevated, normal or low WBC count. Often see anemia at presentation as well as thrombocytopenia. Differential often shows circulating blasts (very immature WBCs). Elevated LDH usually seen. Bone marrow biopsy diagnostic
Signs and Symptoms: pallor, fatigue, fever, anorexia, weight loss, weakness, palpitations, dyspnea on exertion, infection, rash, bleeding, bruising

84. Acute Leukemia
Physical findings: Ecchymoses, bleeding, pallor, tachycardia, tachypnea, hepatosplenomegaly, petechiae, scleral hemorrhage
Management: Rapid recognition of symptoms as those of leukemia is crucial in acute leukemia as patients can decline rapidly and die from infectious complications or hemorrhage. Referral to hematologist for work up and chemotherapy

85. Acute Leukemia

86. Bone Marrow Biopsy

87. Chronic Leukemia
Definition: differs from acute leukemia in that symptoms have lasted more than 3 months. For CML, the natural history of the disease usually includes a chronic phase lasting 2-4 yrs. Accelerated phase can then occur leading to progressive leukocytosis, anemia and thrombocytopenia. Eventually a blast crisis may ensue in which the disease may behave more like AML requiring aggressive therapy and having a poor prognosis
Incidence: 4000 cases in US per year for CML

88. Chronic Leukemia
Lab/diagnostic testing: CBC with diff shows elevated WBC often with basophilia. Anemia often present. Platelets may be normal or low. Usually no peripheral blasts. Marrow blasts elevated or normal. LDH increased. With very high WBC may see hyperkalemia and hypoglycemia. Ultrasound of spleen often done as well as CT scans to help differentiate between leukemia and lymphoma
Signs and Symptoms: may be subtle easy fatigability, malaise, anorexia, abd discomfort and early satiety from enlarged spleen.
Physical findings: may be none, or hepatosplenomegaly, pallor, ecchymoses
Diagnosis made with bone marrow biopsy

89. Chronic Leukemia Management:
CLL: many times a watch and wait approach is taken and only treated if WBC doubling time is < 6m or pt becomes symptomatic with progressive abnormal blood counts. At that point chemotherapy would be offered, usually IV therapy depending on pts age and performance status
CML: Most cases of CML have a genetic 9:22 translocation (termed Philadelphia Chromosome). This type of CML is treated at this time with an oral targeted chemotherapy agent called Gleevec taken daily. There are also new agents being studied for CML that work similar to Gleevec if Gleevec fails.

90. Lymphoma
Definition: Hematologic malignancy involving lymphadenopathy as well as possible bone marrow and other solid organ involvement.
Types: Hodgkin’s Lymphoma and Non-Hodgkin’s Lymphoma (NHL)
Incidence: About 8000 new cases of Hodgkin’s disease are diagnosed each year. Usually occurring in young adults. NHL has an incidence of up to 90,000 new cases per year
Differential Dx: infections causing lymphadenopathy, cat scratch fever, viral infections (HIV), auto-immune disorders, endocrine disorders, sarcoidosis
Lab/diagnostic testing: CBC with diff, CMP, LDH, Beta 2 microglobulin, lymph node biopsy, bone marrow biopsy, CXR, CT scans, PET scan

91. Lymphoma
Risk factors for development of lymphoma: EBV, HHV-8, HTLV-1 viruses have a strong association with development of lymphoid tumors. h.Pylori is a risk factor for development of gastric MALT (mucosa associated lymphoid tissue) lymphoma. Inherited or acquired immunodeficiency disorders also predispose individuals to lymphoma. Increase incidence of NHL in farmers and meat workers. Increased Hodgkin’s disease in wood workers.
Signs and symptoms: Painless adenopathy, fever, night sweats, weight loss, fatigue (B-symptoms)
Physical findings: lymphadenopathy in one or more lymph node chains, hepatosplenomegaly, pallor

92. Lymphoma
Staging: based on number of lymph node chains involved and location above and or below diaphragm, bone marrow status, extra nodal sites of disease, absence or presence of B-symptoms
Stages from IA-IVB
Histiologic subtypes also important in determining aggressiveness of disease which guides treatment plan offered to patient
Less aggressive NHL: follicular center cell
More aggressive NHL: diffuse large cell

93. Lymphoma
Management:
Based on stage, and subtype for Hodgkin’s disease usually IV chemotherapy +/- radiation therapy
NHL treatment can range from watch and wait approach to very strong IV chemotherapy for the aggressive subtypes. Bone marrow transplant is sometimes needed if patient fails initial chemotherapy for aggressive NHL.

94. WBC Differential Five subtypes of WBC noted in differential include:
Neutrophils (segs + bands) AKA granulocytes
these are immature WBC. Important in fighting bacterial infections. Elevated neutrophils can be caused by acute infection, chemotherapy, stress reaction, burns, tissue necrosis, chronic inflammatory disorders. Decreased neutrophils = neutropenia. Increased risk for infection if neutrophils < Severe risk for infection if < 500.
Lymphocytes – elevated or decreased levels can be caused by infection – bacterial or viral, most common cause of increased level >10,000 is CLL. Lymphopenia can be caused by acute stressful illness (MI, pneumonia) as well as steroid therapy and lymphoma

95. WBC Differential
Monocytes – increased in infection, granulomatous disease (sarcoid), collagen vascular disease. Decreased in acute stress reaction, pt on steroids, leukemia, chemo and immunosuppressant therapies
Eosinophils – Increased in allergic diseases, parasitic infections, collagen vascular diseases, from certain medications, leukemia. Decreased in acute stressful illness, steroids
Basophils – Increased in allergic diseases, CML, chronic inflammatory disorders.

97. WBC differential cells

98. Case Studies

99. Case Study #1 History 11 year old male.
Presented in emergency room with recent onset of easy bruising, bleeding gums, and persistent epistaxis.
Previously in excellent health. Mother stated he was "never sick before in his entire life."
No history of recent viral infection, and no family history of bleeding disorders

100. Case Study #1 CBC (with microscopic differential) RBC 4.52 x 1012/L
HGB g/dL
HCT %
MCV fL
MCH pg
MCHC g/dL
RDW
WBC x 109/L
N % L M E B
PLT <5 x 109/L
MPV fL

101. Case Study #1 Morphologic Alterations
Results of the blood smear exam were:
RBC morphology: Normocytic, normochromic
WBC morphology: Within normal limits (one lymphocyte shown here)
PLT morphology: Appear increased in size

102. Case Study #1
1 giant platelet seen

103. Case Study #1 Further Laboratory Studies Bone marrow biopsy:
Aspirate: Erythrocyte and granulocyte maturation within normal limits. Megakaryocytes appear normal in number and morphology.
Sections: Slightly hypocellular for his age, with abundant megakaryocytes.
Coagulation:
INR (RI )PTT sec (RI 23-34)TT sec (RI )

104. Case Study #1 Physical Exam
Bleeding from the left nostril. Numerous petechiae and purpura; mostly on the extremities.
No organomegaly.

105. Case Study #1
What is the most likely diagnosis?

106. Case Study #1
Diagnosis
Immune thrombocytopenic purpura (ITP)

107. Case Study #1 Clinical Course
The patient was given standard therapy for ITP for more than a month, but failed to respond. His platelet counts did not improve and he continued to have severe nosebleeds.
Because the patient's ITP was refractory to treatment, it was decided to perform a splenectomy. During the procedure, he received several units of platelets, and tolerated the surgery well.
His platelet count gradually recovered; after six months it was 289 x 109/L.
He is followed in Hematology Clinic, and continues to do well.

108. Case Study #2 33 year old female.
Immigrated to the United States from Laos four years prior to admission. History obtained through an interpreter.
Multiple transfusions and splenectomy two years prior to admission. Reason and/or diagnosis unclear to patient.
Presented with flu-like symptoms of fever, malaise, epigastric discomfort and nonproductive cough.

109. Case Study #2 CBC (with microscopic differential) RBC 4.15 x 10[12]/L
HGB g/dL
HCT %
MCV fL
MCH pg
MCHC g/dL
RDW
WBC (corrected) x 10[9]/L
N % L M E B
NRBC/100 WBC
PLT x

110. Case Study #2

111. Case Study #2 Morphologic Alterations
Results of the blood smear exam were:
RBC morphology: 3+ hypochromasia 1+ polychromasia 2+ anisocytosis 3+ target cells occ spherocytes and fragments Howell Jolly bodies present
WBC morphology: Within normal limits
PLT morphology: Within normal limits

112. Case Study #2 Hemoglobin electrophoresis: Hemoglobin E 80 %
Hemoglobin F %
Other hemoglobins* 15 %
*Identified as hemoglobin A2, hemoglobin Barts and a hemoglobin H mutant.
Iron studies:
Serum ferritin ng/mL
(RI 12-86)
Serum iron µg/dL
(RI )
TIBC µg/dL
(RI )
Saturation %
(RI 20-55)

113. Case Study #2
Diagnosis
Homozygous hemoglobin E disease and alpha thalassemia
Clinical course
The patient's flu-like symptoms subsided; they were presumed to be viral in origin.
She was referred to the Hematology Clinic, and placed on iron chelation therapy. After 18 months, her serum ferritin had fallen to 114 ng/mL. Her hemoglobin remained in the 7 to 9 g/dL range. Chelation was discontinued, with plans to monitor the ferritin level every six months and resume treatment when needed.

114. Case Study #3 History 39 year old female.
History of fibrocystic breast disease. Seen for routine work-up prior to breast biopsy.
Physical Exam
Moderate splenomegaly. No other organomegaly.

115. Case Study #3 CBC (with microscopic differential) RBC 4.28 x 10[12]/L
HGB g/dL
HCT %
MCV fL
MCH pg
MCHC g/dL
WBC x 10[9]/L
N seg %
N band
N meta
N myelo
N pro L M E B
PLT x 10[9]/L

116. Case Study #3

117. Case Study #3 Morphologic Alterations
Results of the blood smear exam were:
RBC morphology: Normocytic, normochromic
WBC morphology: Mature stages and precursors all within normal morphologic limits
PLT morphology: Within normal limits

118. Case Study #3 Bone marrow biopsy: Aspirate differential (1000 cells):
Erythroblasts %
Myeloblasts N
promyelocytes N and precursors L M E and precursors B and precursors Sections:
Markedly hypercellular with increased megakaryocytes.

119. Case Study #3 Cytochemistry:
Leukocyte alkaline phosphatase[LAP] score: (RI ) Cytogenetics:
46,XX,t(9;22)(q34;q11)[Philadelphia chromosome]seen in all marrow cells analyzed.

120. Case Study #3 Diagnosis: Chronic Myeloid Leukemia (CML)
Clinical Course
Following the standard preparatory regimen, the patient received an allogeneic bone marrow transplant. The donor was her HLA-matched brother.
Her post-transplant course went well, and 28 days later, her hemoglobin was g/dL, WBC 2.0 x 10[9]/L, and PLT 84 x 10[9]/L. Her marrow showed evidence of good engraftment in all three cell lines.
Cytogenetics showed 46,XY normal karyotype in all marrow cells analyzed. No 46,XX cells and no cells with a Philadelphia chromosome were seen.
This patient continues to be followed in Hematology Clinic. At her last visit, ten years post-transplant, she was still doing well and had no evidence of recurrent disease. Molecular diagnostic studies performed at that time were negative for BCR-abl transcripts.

121. Case Study #4 18 year old male student from Nigeria.
Came to the emergency room with symptoms of fever, shaking chills, nausea, and generalized malaise; occurring intermittently over the past five days.
Physical Exam
Fever of 103.3°F. Tachycardia with a heart rate of Otherwise within normal limits

122. Case Study #4 CBC (with microscopic differential) RBC 5.85 x 10[12]/L
HGB g/dL
HCT %
MCV fL
MCH pg
MCHC g/dL
RDW
WBC x 10[9]/L
N % L M E B
PLT x 10

123. Case Study #4

124. Case Study #4 Morphologic Alterations
Results of the blood smear exam were:
RBC morphology: Normochromic Numerous red cells contain intraerythrocytic organisms. Infected RBCs are enlarged; some are oval shaped, others appear somewhat "fimbriated." Doubly infected cells are present, and several morphologic stages can be found, including ring forms, mature schizonts, and gametocytes.
WBC morphology: Within normal limits (one lymphocyte shown here)

125. Case Study #4 PLT morphology: normal
RBC enzyme: G6PD U/g Hgb (RI )

126. Case Study #4 Diagnosis - Malaria
Upon further questioning, the patient stated that he had arrived in the United States from Nigeria approximately six months prior to this visit. Shortly after his arrival, he had experienced a similar illness that was diagnosed as malaria. Medication was prescribed, but once he felt better he did not continue to take it.
Based on the blood smear morphology, the periodic pattern of his fever and chills, and his travel history, the causative organism was identified as Plasmodium ovale.

127. Case Study #4 Clinical Course
The patient was hydrated with normal saline, and started on appropriate treatment for the erythrocytic stages of malaria. Several days later he began a second course of therapy to eliminate the exoerythrocytic (hepatic) forms of the organism. He completed the course of therapy, and on subsequent visits was asymptomatic.
Note: On the basis of his low MCV, his relatively high RBC count, and his ethnic background, it is likely that this patient also has alpha thalassemia trait.

128. Case Study #5 History: 70 year old female.
Symptoms of dyspnea on exertion, easy fatigability, and lassitude for past 2 to 3 months.
Denied hemoptysis, GI, or vaginal bleeding. Claimed diet was good, but appetite varied.
Physical Exam:
Other than pallor, no significant physical findings were noted. Occult blood was negative.

129. Case Study #5 CBC (with microscopic differential) RBC 3.71 x 10[12]/L
HGB g/dL
HCT %
MCV fL
MCH pg
MCHC g/dL
RDW
WBC x 10[9]/L
N % L M E B
PLT x 10[9]/

130. Case Study #5

131. Case Study #5 Morphologic Alterations
Results of the blood smear exam were:
RBC morphology: 2+ hypochromasia 3+ microcytosis 2+ anisocytosis 2+ elliptocytes and target cells occ teardrops and fragments
WBC morphology: Within normal limits (one lymphocyte shown here)
PLT morphology: Within normal limits

132. Case Study #5 Iron studies were performed, and results were:
serum ferritin <10 ng/mL
(RI 12-86)
serum iron µg/dL
(RI )
TIBC µg/dL
(RI )
saturation %
(RI 20-55)

133. Case Study #5 Diagnosis Iron deficiency anemia Clinical Course
Diagnostic procedures included upper GI endoscopy, colonoscopy, and small bowel biopsy. All were negative.
The patient received packed RBC transfusions and was started on iron therapy.
She refused any further laboratory testing or other procedures, and was discharged at her own request. She was lost to follow- up.
The etiology of her iron deficiency anemia could not be determined, but it was most likely nutritional.

134. Case Study #6 History 75 year old male.
Symptoms of severe headache and generalized pruritis.
Physical Exam
Spleen palpable 10 cm. below left costal margin. Liver palpable 3 cm. below right costal margin. The rest of the exam was within normal limits.

135. Case Study #6 CBC (with microscopic differential) RBC 7.70 x 10[12]/L
HGB g/dL
HCT %
MCV fL
MCH pg
MCHC g/dL
RDW
WBC x 10[9]/L
N seg %
N myelocyte % L M E B
PLT x 10

136. Case Study #6

137. Case Study #6 Morphologic Alterations
Results of the blood smear exam were:
RBC morphology: Essentially normocytic, normochromic
WBC morphology: Within normal limits
PLT morphology: Within normal limits

138. Case Study #6 Further Laboratory Studies Bone marrow biopsy:
Aspirate differential: Within normal limits
Sections: Markedly hypercellular for age. Cytogenetics:
46,XY. No numerical or structural chromosome abnormalities detected.
Pulmonary function:
Oxygen saturation: 97% (RI )

139. Case Study #6 Diagnosis Polycythemia vera Clinical Course
The patient is being followed by his local physician, and treated with periodic phlebotomy.

140. Disseminated Intravascular Coagulation (DIC)
DIC is evidence for the simultaneous presence of:
thrombin(procoagulation)
plasmin(fibrinolysis)
Presentations:
an acute hemorrhagic disorder
an indolent, subacute thrombotic disorder

141. Primary Events in DIC Underlying Disorder
Systemic Activation of Coagulation
Widespread
Intravascular
Fibrin Deposition
Consumption of
Platelets and
Clotting Factors
Thrombosis
Bleeding
K. McInerny. American Academy of Pediatrics textbook of pediatric care. 2009

142. Pathophysiology of DIC
Blue (dotted) indicates inhibitors of coagulation
K. McInerny. American Academy of Pediatrics textbook of pediatric care. 2009

143. Disseminated Intravascular Coagulation (DIC) Mechanism
Systemic activation
of coagulation
Depletion of platelets
and coagulation factors
Intravascular
deposition of fibrin
Thrombosis of small
and midsize vessels
with organ failure
Bleeding

144. Common clinical conditions associated with DIC
Vascular disorders
Reaction to toxin (e.g. snake venom, drugs)
Immunologic disorders
Severe allergic reaction
Transplant rejection
Sepsis
Trauma
Head injury
Fat embolism
Malignancy
Obstetrical complications
Amniotic fluid embolism
Abruptio placentae

145. Etiology of DIC Acute DIC Subacute DIC
Infection: Gram -ve sepsis, viremia, parasitic
Obstetric: Abruption, amniotic fluid embolism, eclampsia
Malignancy: Acute promyelocytic leukemia
Trauma: Crush injury, freshwater drowning, heat stroke, snakebite
Other: Homozygous protein C and S deficiency (infants), severe liver disease, HIT
Subacute DIC
Malignancy: mucinous adenocarcinoma (Trousseau syndrome)
Obstetric: retained dead fetus
Vascular: hemangioendothelioma (Kasabach-Merritt), venous thromboembolic disease, chronic renal failure

146. Post-varicella purpura fulminans
DeLoughery, ASH Image Bank, 2004

147. Diagnosis of DIC Screening tests: Confirmatory tests:
Activated partial thromboplastin time (prolonged)
Prothrombin time (prolonged)
Fibrinogen (decreased)
Platelet count (decreased)
Confirmatory tests:
D-dimer (elevated)
Fibrin degradation products (elevated)

148. Mechanisms In Hematology Israel

149. Value of the D-dimer
Measure of D-dimers liberated from fibrin by action of plasmin
Evidence of prior thrombin activity followed by fibrinolysis
Should be part of evaluation of DIC
Also now an important screening and prognostic tool in venous thromboembolic disease
Good positive predictive value for DVT and PE
Very high negative predictive value
Source: Wells et al., NEJM, 2003;349:
Eichinger et al., JAMA, 2003;290:

150. Treatment of DIC Treat the underlying condition first!
Antibiotics, surgery, chemotherapy, embolization
disease-specific therapy
APML - all trans-retinoic acid (ATRA)
Replacement therapy
Platelets, FFP, cryoprecipitate
Heparin
May be useful in certain situations
Acral cyanosis and digital ischemia, purpura fulminans, retained dead fetus, migratory thrombophlebitis

151. Von Willebrand disease
Von Willebrand disease is caused by a deficiency of von Willebrand factor. Von Willebrand factor helps blood platelets clump together and stick to the blood vessel wall, which is necessary for normal blood clotting. There are several types of Von Willebrand disease.
A family history of a bleeding disorder is the primary risk factor.

152. Von Willebrand disease
Symptoms
Abnormal menstrual bleeding
Bleeding of the gums
Bruising
Nosebleeds
Skin rash

153. von Willebrand Disease Clinical features
von Willebrand factor Carrier of factor VIII
Inheritance Autosomal dominant
Incidence 1/10,000
Clinical features Mucocutaneous bleeding

154. Laboratory evaluation of von Willebrand disease
Classification
Type 1 Partial quantitative deficiency
Type 2 Qualitative deficiency
Type 3 Total quantitative deficiency
Diagnostic tests:
vonWillebrand type
Assay
vWF antigen ß Normal ßß
vWF activity ß ß ßß
Multimer analysis Normal Normal Absent

155. Treatment of von Willebrand disease Varies by Classification
Cryoprecipitate
Source of fibrinogen, factor VIII and VWF
Only plasma fraction that consistently contains VWF multimers
Correction of bleeding time is variable
DDAVP (Deamino-8-arginine vasopressin)
Increases plasma VWF levels by stimulating secretion from endothelium
Duration of response is variable
Used for type 1 disease
Dosage 0.3 µg/kg q 12 hr IV
Factor VIII concentrate (Humate-P)
Virally inactivated product
Used for type 2 and 3