1. Blood disorders

2. What is hematology?
Hematology is the study of blood and is concerned mainly with the formed elements in the blood.
The formed elements in the blood include:
The white blood cells (leukocytes) which include the neutrophils, eosinophils, basophils, monocytes, and lymphocytes (.
The red blood cells (erythrocytes)
The platelets (thrombocytes)
All of the formed elements in the blood are derived from same pluripotential stem cell in the bone marrow

3. What is hematology continued
Erythrocytes function in the transport of oxygen to the tissues.
Leukocytes function in both specific (immune responses) and non-specific defenses against foreign invasion.
Thrombocytes function in hemostasis or blood clotting.

4. Hemostasis
Disorders of bleeding
Anemia
Blood malignancies

5. Hemostasis

6. definition
Maintenance of fluidity of blood while in vessel and formation of hemostatic plug on vascular injury

7. Balance between clot formation and bleeding is maintained

8. Hemostasis involves
Clot formation
Anti clotting mechanisms

9. At a site of a vascular injury
1.Vasoconstriction
2.Primary hemostatic plug formation
3.Secondary hemostasis due to activation of coagulation cascade by tissue factor and phospholipid via extrinsic pathway- the end result being fibrin which traps the cells in the blood forming a clot

11. Vasoconstriction
due to local neural response, and release of endothelin from the endothelium vessels constricted

12. Primary hemostatic plug formation
due to platelet adhesion
activation
degranulation(ADP, TXA2)
recruitment of other platelets

13. In a site of vessel wall injury platelets in circulation comes in to contact with the ECM
On contact with ECM constituents, platelets undergo 3 reactions:
1) ADHESION and shape change
2) SECRETION (release reaction)
3) AGGREGATION

14. PLATELET ADHESION
To sub-endothelial ECM constituents
Bridged by vWF, a product of endothelial cells

15. PLATELET SECRETION
Occurs soon after adhesion
Platelets release ADP and calcium
ADP activation of platelets is essential for platelet aggregation, further release of ADP

16. Platelet aggregation
product of platelet set up a reaction leading to build-up of an enlarging platelet aggregate, the primary hemostatic plug

17. Vascular and platelet responses are important in reducing bleeding but their activity is limited.
To arrest bleeding the proper ‘clot’ should be formed
This is brought about by the clotting cascade

18. Coagulation cascade
The coagulation cascade is essentially a series of enzymatic conversions, turning inactive proenzymes into activated enzymes and culminating in the formation of thrombin.
Thrombin then converts the soluble plasma protein fibrinogen into the insoluble fibrous protein fibrin.
This results in formation of the definitive clot

20. Anti clotting mechanism
Once activated the coagulation cascade must be restricted to the local site of vascular injury to prevent clotting of the entire vascular tree.
Regulated by natural anticoagulants
Anti thrombin III
Protein C and Protein S
Tissue palsminogen
With onset of coagulation cascade, fibrinolytic cascade is also activated to limit the the size of final clot
Primarily accomplished by plasmin

22. Disorders of hemostasis
Clot formation inappropriately
-thrombosis
Bleeding disorders

23. Bleeding disorders

24. Types of skin bleeds –terminology
Petechie - Minute (1- to 2-mm) hemorrhages into skin, mucous membranes, or serosal surfaces

25. Types of skin bleeds –terminology
Purpuras - Slightly larger i.e 3- to 5-mm hemorrhages are called purpuras

26. Types of skin bleeds –terminology
Ecchymoses - Larger i.e 1- to 2-cm or more subcutaneous hematomas (bruises)

27. Bleeding disorders Vessel wall disorders Platelet disorders
Coagulation disorders

28. Vessel wall disorders
Defective collagen due to connective tissue disorders, vitamin C deficiency

29. Platelet disorders Low platelet count (thrombocytopenia )
Platelet function disorders

30. Causes of thrombocytopenia
Decreased platelet production
-bone marrow disorders like cancers,aplastic anemia,
-drugs, infections
Increased destruction
-immune thrombocytopenic purpura
-DIC
-HUS
Enlarged spleen

31. Coagulation disorders
Hemophilia A
Hemophilia B
Vitamin K deficiency
Von Willebrand Disease

32. Platelet and vessel wall defects usually present as
skin and mucous membranes-Petechie,Ecchymosis
Gum bleeding and epistaxis
Menorrhagia
Gastrointestinal bleeding
Intracranial bleeding

33. Clotting factor disorders may present as
Bleeding Into joints - Haemarthroses
Into deep tissues – Hematoma
Muscle bleeds

34. Coagulation disorders
Hemophilia A
Hemophilia B
Vitamin K deficiency
Von Willebrand Disease

35. Question
why does vitamin K deficiency give rise to bleeding?

36. Hemophilia A & B clinically similar:
occur in approximately 1 in 5,000 male births
account for 90% of congenital bleeding disorders
Hemophilia A is approximately 5 times more common than B

37. Etiology
Inherited as a sex linked recessive trait with bleeding manifestations only in males
genes which control factor VIII and IX production are located on the x chromosome; if the gene is defective synthesis of these proteins is defective
female carriers transmit the abnormal gene
A disease of males

39. Classification % normal factor level Causes of bleeding Severe < 1%
bleeding after trivial injury or spontaneous
Moderate
1 - 5%
bleeding after minor injury; occasional spontaneous bleeds
Mild %
following major trauma, surgical or dental procedures

40. Diagnosis
Atypical bleeding at circumcision or bruising at neonatal vaccines
Toddlers with lip bleeding or unusual bruising when learning to walk
Hx of affected males on mother’s side
Elevated PTT
Factor assays

41. Clinical Features – Joint Bleeds
Joints (Hemarthrosis)
Knees, ankles and elbows most common sites
begin as the child begins to crawl and walk
Single joint bleed: stiffness, swelling, pain
With repeated bleeding into same jt---arthropathy-> stiffness and contractures

43. Clinical Features – Muscle Bleeds
Bleeding into muscle or soft tissue
Sites: calf
Symptoms: pain, swelling, muscle spasm
Complications: nerve compression, contracture

44. Other Sites of Hemorrhage
Abdomen
GI tract
Intracranial bleeds
Around vital structures in the neck
Can cause death…

45. They have high risk of HIV,Hep B and Hep C due to repeated transfusion of blood products

46. Management Specific Hemophillia A Fac viii preparations Cryo DDAVP
Hemophillia B
Fac ix
CPP

47. General Avoid NSAIDs Avoid contact sports Avoid IM injections
Good dental care
Education – life long management
Acute and long term management of musculoskeletal problems

48. Von Willabrand disease
Read…..

49. Investigations in bleeding disorders
Bleeding time-vessel wall and paltelet defects detected
Prothrombin time (PT)-prolonged in disorders of the extrinsic pathway
Activated partial thromboplastin time(APTT) –prolonged in intrinsic pathway disorders

51. Thank you…..