1. Blood Coagulation

2. Haemostasis part2

5. ROLE OF ENDOTHILIUM

7. Stable Hemostatic Plug
Hemostasis:
BV Injury
Tissue Factor
Neural
Coagulation
Activation
Blood Vessel
Constriction
Platelet
Activation
Primary hemostatic plug
Reduced
Blood flow
Plt-Fusion
Thromibn,
Fibrin
Stable Hemostatic Plug

8. Prothrombin Thrombin
Coagulation:
Intrinsic 12,11,9,8
(aPTT-)
Extrinsic-7
(PT)
Common Path (TT)
FX  FXa
Prothrombin Thrombin
Fibrinogen  Fibrin

9. Clot formation & retraction
Fibrinogen
Thrombin
F-XIIIa
Fibrin Mononer
Fibrin Polymer
Cross Linked
Fibrin

10. clot Procoagulant Profibrinolytic Anticoagulant Antifibrinolytic
Platelets
Factors
Fibrinogen
von Willebrand Factor
Profibrinolytic
Plasminogen
tPA
Fibrin Fragment D-dimer
FORMATION
RESOLUTION
clot
Anticoagulant
Antithrombin III
Protein C
Protein S
Antifibrinolytic
PAI-1
Alpha-2 Antiplasmin

12. Role of thrombin

13. Fibrinolysis

17. Coagulation Made Easy- The Mixing Study
Useful to differentiate etiologies of prolonged clotting in a coagulation assay.
Patient’s plasma is mixed 50:50 with normal plasma. Coagulation assay is repeated.
If “substantial” correction is noted after mix, suspect clotting factor deficiency.
If no or minimal correction seen, suspect inhibitor.

18. Disorders of the haemostatic mechanism are devided into three main groups:
Disorders of the vessels
Disorders of the platelets
Disorders of the coagulation mechanism („coagulopathies”)
„ purpuric diseases”

19. The investigation of a patient with a suspected disorder of haemostasis
case history (personal details, family history)
inspection (type of bleeding)
physical examination
other known diseases
drugs and medications
laboratory tests

20. The main symptom of all diseases is the bleeding:
Certain signs and symptoms are virtually diagnostic of disordered haemostasis.
The main symptom of all diseases is the bleeding:
● in the „purpuric disorders” cutaneous and mucosal bleeding usually is prominent
● in different types of „coagulopathies” hemarthroses, haematomas are the characteristic bleeding manifestations.
The onset of bleeding following trauma frequently is delayed (recur in a matter of hours) (the temporary hemostatic adequacy of the platelet plug may explain this phenomenon).

21. Petechiae, purpuras: small capillary haemorrhages ranging from the size of a pinhead to much larger

22. Petechiae, purpuras

23. Haematomas: may be spontaneous (in a serious hemorrhagic disease) or may occur after trauma (in a mild hemorrhagic disease).

24. Haematomas

25. Intramuscular injection may be very dangerous to the patient with a bleeding disorder
Venipuncture (if skilfully performed) is without danger becouse the elasticity of the venous walls.

26. Bleeding Disorders

27. Coagulopathies
Aquired: generally several coagulation abnormalities are present. Clinical picture is complicated by signs and symptoms of the underlying disease  Deficiencies of the vitamin K dependent coagulation factors (FII, VII, IX, X)  Hepatic disorders  Accelerated destruction of blood coagulation (DIC)  Inhibitors of coagulation  Others (massive transfusion, extracorporal circulation)
Hereditary: deficiency or abnormality of a single coagulation factor.
Hemofilia A (FVIII)
Hemofilia B (FIX)
Von Willebrand’s disease
Rare coagulopathies (FI. II. V. VII. X. XI. XIII)

28. Hereditary Factor Deficiencies Hemophilia
x-linked recessive conditions (males only)
type A : F VIII:C deficiency (Classical Hemophilia)
B : F IX deficiency (Christmas disease)
C : F XI deficiency
unexplained bruising or bleeding in young males, usually ~ 1 yr of age
joint & muscle bleeding → arthropathy

29. Haemophilia
A bleeding disorder in which clotting factor VIII (eight) /Haemophilia A/ or IX (nine) /Haemophilia B/ in a person's blood plasma is missing or is at a low level.
Prevalence:
haemophilia A: 105/million men
haemophilia B: 28/million men

30. In haemophilia, VIII or IX clotting factor is missing, or the level of that factor is low.
This makes it difficult for the blood to form a clot, so bleeding continues longer than usual.

31. The hemophilia gene is carried on the X chromosome  in males who lack a normal allele, the defect is manifested by clinical haemophilia. Women may be carriers.

32. Haemophilia is a lifelong disease
A person born with haemophilia will have it for life.
The level of factor VIII or IX in his blood usually stays the same throughout his life.

34. hemophilia A

35. Hereditary Factor Deficiencies Hemophilia
■ screening: prolonged PTT
■ hemophilia A
mild
moderate
severe : life-threatening (CNS bleed)
treatment
factor replacement
rFVIIa

36. Factor VIII Concentrate Necessary for Hemostasis
(% of normal)
Spontaneous hemorrhage
1-3 %
Moderate trauma
4-8 %
Hemarthrosis/deep skeletal muscle hemorrhage
10-15 %
Major surgery
> 30%

37. Hemophilia B (Christmas disease, Factor IX def.)
less common than hemophilia A
similar clinical Sx and inheritance pattern as hemophilia A (sex-linked)
XII XI IX
VIII
VII X V II I
XIII
Stable clot

38. von Willebrand’s disease
easy bruisability (no bleeding into joints)
unable to release VIII-vWF
intact VIII-vWF synthesis
VIII-C level is also decreased (unknown reason)
autosomal dominant
1 in 30,000 population
usually diagnosed in childhood or young adults
increased bleeding time
normal plt, PT
normal or increased aPTT

39. Hereditary Platelet Disorder von Willebrand Disease (vWD)
most common congenital bleeding disorder
quantitative or qualitative abn. of vWF
Type 1: most common form
partial quantitative deficiency of vWF
autosomal dominant
mucocutaneous bleeding
hematology consult prior to surgery
prolonged bleeding time, normal platelet

40. Hereditary Platelet Disorders von Willebrand Disease (vWD)
Type 2: qualitative alterations in the vWF structure
& function
Type 3: least common and most severe
Complete absence of vWF in plasma or storage organelle
Autosomal recessive
acquired vWD
Lymphoproliferative disease ▪ cardiac/valvular disease
Tumors ▪ medications (valproic acid)
Autoimmune disease ▪ hypothyroidism

41. Hereditary Platelet Disorders von Willebrand Disease
Treatment: Desmopressin (DDAVP)
synthetic analog of vasopressin
↑ both F VIII and vWF 3 - 5x in 30 mins
preop prophylactic dose: 0.3 mcg/kg IV in ml NS infused mins q hrs PRN
duration 8-10 hrs
intranasal dose: 300 mcg – for home treatment, not for preop prophylaxis

42. Hereditary Bleeding Disorders von Willebrand Disease
DDAVP
vasomotor effect: flushing, ↑HR, headache
SE: hyponatremia, seizures
not for children < 3 yrs old
unresponsive to DDAVP (15%)
cryoprecipitate
FFP
factor VIII / vWF concentrate

43. Vitamin K Deficiency vitamin K dependent factors : II, VII, IX, X
acquired disorder
may occur in malnutrition, malabsorption, biliary obstruction, drug
increased PT
normal bleeding time, plt
normal or increased aPTT
XII XI IX
VIII
VII X V PT II I
XIII
Stable clot

44. Severe Liver Disease factors synthesized in liver : II, V, VII, IX, X, fibrinogen
XII
increased PT, aPTT
normal bleeding time, plt XI IX
VIII
VII X V
aPTT PT II I
XIII
Stable clot

45. Platelet Dysfunction, Factor Deficiencies & Presence of Inhibitors
Liver disease
• synthesis of coagulation factors (except VIII),
anticoagulants, ATIII, protein C & S, plasminogen
• clearance of activated clotting factors, tPA, FDPs
DIC

46. Blood Component Therapy Transfusion of FFP
1) replacement of isolated factor deficiency
2) reversal of coumadin
3) antitrombin III deficiency
4) treatment of immunodeficiencies
5) treatment of TTP
6) massive blood transfusion

47. Blood Component Therapy Cryoprecipitate
contains significant levels of factor VIIIC, factor VIII: vwF, XIII, fibrinogen
indications:
1) hemophilia
2) von Willebrand disease
3) fibrinogen deficiencies
4) uremic platelet dysfunction

48. Coagulopathies

49. Disseminated Intravascular Coagulation (DIC)
- an acute, subacute, or chronic thrombohemorrhagic disorder occurring as a secondary complication in a variety of diseases
- activation of clotting system resulting in wide spread formation of microthrombi throughout the microcirculation
- as a consequence, causing consumption of platelets, fibrin and coagulation factors, and activation of thrombolytic mechanism
Two major triggering mechanisms
1. release of tissue factor or thromboplastic substance
2. widespread endothelial injury

50. DIC Triggering Mechanisms
1. release of tissue factor or thromboplastic substance
- placental tissue
- granules from leukemic cells
- bacterial endotoxin
- mucus from adeno CA
2. widespread endothelial injury
- Ag-Ab immune complex deposit
- extreme temperature
- microorganisms

51. DIC Pathology: - wide spread thrombi
(brain, heart, lungs, kidneys, adrenals, spleen , liver)
- microinfarcts
Clinical: - ~50% associated with obstetric complications
- ~30% with carcinomatosis
- microangiopathic anemia
- dyspnea, cyanosis
- convulsions, coma
- oliguria, acute renal failure
- shock, circulatory failure

52. DIC
Clinical: acute DIC with a predominance of thrombin generation and consumption of coagulation factors
bleeding tendency
(oozing from venopuncutres or operating site)
subacute and chronic DIC
thrombotic tendency