Blood disorders

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 hemostaticplug 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 -thromosis • 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 defficiency

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 perpura -DIC -HUS/TTP • 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 - Hemarthroses • Into deep tissues – Hematoma • Muscle bleeds

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

35. Question • why dose vitamin K defficiency 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

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: iliopsoas, 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