Hematopathology.pptx

Hematopathology or hemopathology is the study of diseases and disorders affecting and found in blood cells, their production, and any organs and tissues involved in hematopoiesis, such as bone

1. Hematopathology

2. Lecture objectives: Hemostatic disorders Coagulopathies Clinical presentation Complications Investigations

3. BLEEDING DISORDERS characterized by abnormal bleeding( spontaneously or induced) main contributors are :the vessel wall, the platelets, and the clotting factors. Bleeding disorders may arise from abnormalities of vessels, platelets, or coagulation factors, alone or in combination

4. investigations of coagulopathies : Prothrombin time (PT) assesses the extrinsic and common coagulation pathways. prolonged PT : deficiency of factor V, VII, or X or prothrombin or fibrinogen, or by an acquired inhibitor (an antibody) Partial thromboplastin time (PTT). assesses the intrinsic and common coagulation pathways. prolonged PTT : deficiency of factor V, VIII, IX, X, XI, or XII or prothrombin or fibrinogen, or by an acquired inhibitor . Platelet count . Tests of platelet function: Platelet aggregation , bleeding time. clotting factors assay

5. Features that may distinguish bleeding In coagulation defects from that in platelet disorders

6. Bleeding due to vascular fragility: Vitamin C deficiency (scurvy) systemic amyloidosis chronic glucocorticoid use, rare inherited conditions affecting the connective tissues, infectious and hypersensitivity vasculitides ( meningococcemia, infective endocarditis ,the rickettsial diseases, typhoid, Henoch-Schönlein purpura . ) “spontaneous” appearance of petechiae and ecchymoses in the skin and mucous membranes

7. DEFECTS IN PLATELETS: T hrombocytopenia( quantitaive ) : important cause of bleeding. Q ualitative ( function ): ( in uremia , certain myeloproliferative disorders ,aspirin ingestion, VWF disease ) Presentation: easy bruising, Nose bleeds, excessive bleeding from minor trauma. menorrhagia .

8. THROMBOCYTOPENIA: count less than 150,000 platelets/ µL counts less than 20,000 platelets/ spontaneous bleeding petechiae or large ecchymoses in the skin, the mucous membranes hemorrhages into the central nervous system are a major hazard

9. IMMUNE THROMBOCYTOPENIC PURPURA : (ITP) Antibodies against platelet membrane glycoproteins IIb / IIIa or Ib /IX complexes The spleen is an important site of anti- platelet antibody production and the major site of destruction Acute ITP : self-limited . seen mostly in children after viral infections Chronic ITP : affect women between the ages of 20 and 40 years. The bone marrow increased numbers of megakaryocytes , petechiae , easy bruising, epistaxis , gum bleeding , menorrhagia and hemorrhages after minor trauma. intracerebral or subarachnoid hemorrhages diagnosis :clinical features, thrombocytopenia, BM, antiplatelet antibodies are not available.

10. Thrombotic Microangiopathies : Thrombotic Thrombocytopenic Purpura and Hemolytic Uremic Syndrome: TTP :presented by fever, thrombocytopenia, microangiopathic hemolytic anemia, transient neurologic deficits, and renal failure. HUS : microangiopathic hemolytic anemia and thrombocytopenia &absence of neurologic symptoms, dominance of acute renal failure, and frequent occurrence in children Fundamental to both is the widespread formation of platelet-rich thrombi in the microcirculation. The consumption of platelets leads to thrombocytopenia , and the narrowing of blood vessels by thrombi results in a microangiopathic hemolytic anemia

11. Cont. PATHOGENESIS TTP : deficient in the metalloprotease ADAMTS 13( enzyme degrades very-high-molecular weight multimers of von Willebrand factor ( vWF ));. ADAMTS 13 deficiency can be inherited or acquired by way of autoantibodies that bind and inhibit it HUS. Most cases in children and elderly persons E. coli strain O157:H7. (Shiga-like toxin) that damages endothelial cells, which initiates platelet activation and aggregation. bloody diarrhea, followed a few days later by acute renal failure and microangiopathic anemia. Recovery is possible with plasma exchange,

12. COAGULATION DISORDERS PT, PTT, or both are prolonged. petechiae and mucosal bleeding are usually absent. , hemorrhages tend to occur in the joints of the lower extremities. Massive hemorrhage may occur after surgery , dental procedures , or severe trauma inherited coagulation disorders : hemophilias ,. von Willebrand disease acquired coagulation disorders :DIC , others in DIC : both thrombocytopenia and coagulation factor deficiencies contribute to bleeding, in von Willebrand disease, a both platelet function and (to a lesser degree) coagulation factor function are abnormal.

13. Causes of acquired coagulation disorders: acquired deficiencies of clotting factors are most common and often involve several factors vitamin K deficiency (required for the synthesis of prothrombin F II & VII, IX, X(10972)) Liver diseases DIC autoantibodies to a single factor.

14. Hemophilia A—Factor VIII Deficiency the most common hereditary cause bleeding. X-linked recessive primarily affects males. Female carriers 30% of cases are caused by new mutations; 70% there is a positive family history.

15. Easy bruising and massive hemorrhage after trauma or operative procedures. Petechiae are characteristically absent “spontaneous” hemorrhages, particularly the joints, ( hemarthroses ) lead to progressive deformities that can be crippling. assays for factor VIII prolonged PTT Hemophilia A is treated with factor VIII infusions of recombinant factor VIII 15% of pt replacement therapy is complicated by the development of neutralizing antibodies against factor VIII,

16. Hemophilia B—Factor IX Deficiency: indistinguishable clinically from hemophilia A less common. The PTT is prolonged. assays of factor IX. It is treated by infusion of recombinant factor IX

17. von Willebrand Disease: Autosomal dominant disorder. spontaneous bleeding from mucous membranes, excessive bleeding from wounds, and menorrhagia . It very common in European descent. Compound defects in platelet function and coagulation, but in most cases only the platelet defect produces clinical findings. The classic and most common variant of von Willebrand disease (type I) is an autosomal dominant disorder in which the quantity of circulating vWF is reduced.

18. DISSEMINATED INTRAVASCULAR COAGULATION (DIC): occurs as a complication of a wide variety of disorders. DIC is caused by the systemic activation of coagulation and results in the formation of thrombi throughout the microcirculation. As a consequence, platelets and coagulation factors are consumed and, secondarily, fibrinolysis is activated. DIC can give rise to either tissue hypoxia and micro infarcts the depletion of the elements required for hemostasis (hence the term consumptive coagulopathy ).

19. DIC is most often associated with : sepsis, obstetric complications, malignancy, and major trauma (especially trauma to the brain).

20. PATHOGENESIS: DIC usually is triggered by either (1) the release of tissue factor or thromboplastic substances into the circulation or (2) widespread endothelial cell damage Thromboplastic substances can be released into the circulation from a variety of sources—for example: the placenta cancer cells Cancer cells can also provoke coagulation in other ways,such as by releasing proteolytic enzymes and by expressing tissue factor.

21. DIC consequences: widespread fibrin deposition within the microcirculation. That lead to ischemia and hemolysis ( microangiopathic hemolytic anemia). Bleeding diathesis results from the depletion of platelets and clotting factors Plasmin cleaves not only fibrin ( firinolysis ) but also factors V and VIII, thereby reducing their concentration further. firinolysis creates fibrin degradation products. Which inhibit platelet aggregation, & have antithrombin activity,

22. Clinical Course: acute DIC is dominated by a bleeding diathesis, chronic DIC (e.g., as occurs in those with cancer) tends to manifest with signs and symptoms related to thrombosis. The abnormal clotting usually is confined to the microcirculation, shock acute renal failure dyspnea , cyanosis, convulsions, and coma. prolonged and copious postpartum bleeding & petechiae and ecchymoses on the skin. Laboratory evaluation reveals thrombocytopenia and prolongation of the PT and the PTT and FDPs.