Hematology lecture 2.pptx

Hematology 2 Platelet disorders Congenital abnormalities of platelets can be divided into disorders of platelet production and those of platelet function. In general they cause moderate to severe bleeding problems Acquired abnormalities decreased production of platelets due to suppression or Fai...

Hematology 2 Platelet disorders Congenital abnormalities of platelets can be divided into disorders of platelet production and those of platelet function. In general they cause moderate to severe bleeding problems Acquired abnormalities decreased production of platelets due to suppression or Failure of the bone marrow the commonest cause of thrombocytopenia.  aplastic anaemia, leukaemia marrow infiltration,  after chemotherapy,  secondary to drug toxicity (penicillamine, cotrimoxazole), alcohol, or viral infection (HIV, infectious mononucleosis). Increased platelet consumption may be due to immune or non-immune mechanisms. Idiopathic thrombocytopenic purpura(ITP) • (ITP) is a relatively common disorder and is the most frequent cause of an isolated thrombocytopenia without anaemia or neutropenia. • In adults it often presents insidiously, most frequently in women aged 15-50 years and can be associated with other autoimmune diseases, in particular systemic lupus erythematosus • In children the onset is more acute and often follows a viral infection. • The autoantibody produced is usually IgG, directed against antigens on the platelet membrane Post-transfusion purpura • (PTP) is a rare complication of blood transfusion. It presents with severe thrombocytopenia 7-10 days Heparin-induced thrombocytopenia (HIT) • occurs during unfractionated heparin therapy in up to 5% of patients, but is less frequently associated with low molecular weight heparins. • It is thought to be due to the formation of antibodies to heparin that are bound to platelet factor 4, a platelet granule protein. • The immune complexes activate platelets and endothelial cells, resulting in thrombocytopenia and thrombosis coexisting. thrombotic thrombocytopenic purpura (TTP) the presenting features can be fever, fluctuating neurological signs, renal impairment, and intravascular haemolysis, resulting in thrombocytopenia. • Recent evidence suggests that the condition is caused by an autoantibody to a protease enzyme which is responsible for cleaving the of von Willebrand factor. The development of this antibody causes intravascular platelet agglutination in vivo and the precipitation of a microangiopathic haemolytic anaemia. • The demonstration of an abnormal pattern of von Willebrand multimers will make the diagnosis highly likely Disseminated intravascular coagulation • usually occurs in critically ill patients as a result of catastrophic activation of the coagulation pathway, often due to sepsis. • Widespread platelet consumption occurs causing thrombocytopenia. Aspirin, non-steroidal anti-inflammatory agents, and glycoprotein IIb/IIIa antagonists • are the most common cause of acquired platelet dysfunction. For this reason aspirin and the IIb/IIIa antagonists are used therapeutically as antiplatelet agents. Coagulation Disorders • Following an injury to blood vessels several actions may help prevent blood loss, including Steps in Hemostasis • A. Vasoconstriction • B. Primary hemostasis (Platelet plug formation) • C. Secondary hemostasis (Fibrin clot formation) • D. Clot Retraction • E. Clot Dissolution Local vasoconstriction • is due to local spasm of the smooth muscle (symp. reflex) • can be maintained by platelet vasoconstrictors. Formation of platelet aggregate • Injured blood vessel releases ADP, which attracts platelets (PLT) • PLT comming in contact with exposed collagen release: serotonin, ADP, TXA2, which accelerate vasoconstriction and causes PLT to swell and become more sticky Formation of blood clot • In the formation of the clot, an enzyme called thrombin converts fibrinogen into insoluble protein, fibrin • Fibrin aggregates to form a meshlike network at the site of vascular damage Tests to evaluate coagulation • PT/INR is sensitive to factors (F) I, II, VII, V, and X. • APTT to F I, II, V, VIII, IX, X, XI, and XII. Prolonged Prothrombin Time (PT) • A prolonged prothrombin time indicates a deficiency in any of factors VII, X, V, prothrombin, or fibrinogen. • vitamin K deficiency (vitamin K is a co-factor in the synthesis of functional factors II (prothrombin), VII, IX and X) or a liver disease (the liver is the site of synthesis of the plasma protein factors). Partial Thromboplastin Time(PTT) • PTT measures the integrity of the intrinsic system (Factors XII, XI, VIII, IX) and common clotting pathways. • Increased levels in a person with a bleeding disorder indicate a clotting factor may be missing or defective. • Liver disease decreases production of factors, increasing the PTT. Congenital disorders of Hemostasis: • Haemophilia A and B are rare conditions with a combined incidence of about 1:10 000 of the population. • They are due to a deficiency of coagulation factors VIII (haemophilia A) and IX (haemophilia B). • As the genes for both proteins are on the X chromosome, both haemophilias have sex-linked inheritance the daughters of a man with haemophilia are therefore obligate carriers. • Patients with severe haemophilia (less than 2% factor VIII or IX) have spontaneous bleeding into muscles and joints that can lead to a crippling arthropathy. • Patients with moderate (2-5%) and mild (5%) conditions usually bleed only after trauma or surgery. • Management is highly specialized and consists of preventing or treating bleeding episodes with plasma-derived or recombinant clotting factors. Acquired disorders of Hemostasis • Most proteins of the coagulation cascade and their regulators and inhibitors necessary for haemostasis are synthesised in the liver. Acquired abnormalities can be due to • impaired synthesis, • increased consumption, or • rarely the formation of autoantibodies against coagulation proteins. • Liver disease can cause a severe bleeding disorder, with prolongation of the prothrombin time particularly, often with coexistent thrombocytopenia due to excessive pooling of platelets in an enlarged spleen. • Malabsorption of vitamin K from the gut can cause a coagulation disorder similar to that caused by ingestion of warfarin. • Overwhelming bacterial infections—for example, meningococcal septicaemia or disseminated malignancies (such as prostatic, pancreatic, and acute promyelocytic leukaemia)— are the most common causes. • Renal disease causes a variable bleeding disorder primarily due to platelet dysfunction • advancing age, • Prolonged use of steroids, and vitamin C deficiency can all result in excessive bruising. Anticoagulants Warfrin monitoring : INR target is 2.5 (target range 2.0 – 3.0). INR testing: • Regular testing of the INR is essential for all people taking warfarin. • Any patient on warfarin should be aware of the risks and early warning signs of bleeding, and they should be followed closely, during the first three months in particular, to ensure that the INR does not exceed 3.0. • Antidote of warfarin is Vitamin K Direct oral anticoagulants (DOACs) Have several advantages over vitamin K antagonists, including no need for laboratory monitoring and  less interference from diet and drugs Low risk of bleeding. THANKS