Disorders of Haemostasis 2024.PDF

Disorders of Haemostasis Normal haemostasis Major types of haemostatic disorders Abnormalities of blood platelets Disorders of blood coagulation Learning outcomes To understand the normal haemostasis and major types of haemostatic disorders To describe the common abnormalities of blood platelets To...

Disorders of Haemostasis Normal haemostasis Major types of haemostatic disorders Abnormalities of blood platelets Disorders of blood coagulation Learning outcomes To understand the normal haemostasis and major types of haemostatic disorders To describe the common abnormalities of blood platelets To explain the main disorders of blood coagulation Disorders of Haemostasis Normal haemostasis Major types of haemostatic disorders Abnormalities of blood platelets Disorders of blood coagulation Haemostasis Clotting mechanisms thus: Clot lysis Internal and external bleeding controlled Pathological thrombosis prevented Several factors act to maintain this equilibrium : Blood vessel – vasoconstriction Platelets – initial haemostatic plug Blood coagulation – fibrin; permanent haemostatic plugs Fibrinolysis – plasmin to remove fibrin thrombi Role of platelets Main function: Early phase of haemostasis via Adhesion −Attracted to exposed collagen −Activation: release of cytoplasmic granules Aggregation − Accumulation/aggregation of large numbers of platelets to form haemostatic plug Blood coagulation Plasma precursors haemostatic plug fibrin permanent Activation of a series of clotting factors normally present in an inactive form Thrombin - key enzyme Some factors are serine proteases Many clotting factors are synthesised in the liver Some (II, VII, IX, X) require Vit K for their synthesis Coagulation Cascade Contact with damaged vessel XII XIIa XI Intrinsic IX pathway Tissue damage XIIa XIa Tissue thromboplastin (III) IXa VIII Ca2+ PL X Ca2+ Ca2+ Extrinsic VII pathway VIIa Ca2+ Xa V PL feedback Common pathway Ca2+ Different colour II IIa I activates Ia XIII Stable fibrin Fibrinolysis Fibrin Plasminogen t-PA Plasmin XIIa, IIa Fibrin-degradation products t-PA : tissue plasminogen activator Clinical laboratory testing for haemostasis Clinical laboratory testing is a critical element in the diagnosis and treatment of haemostatic disorders A vast array of laboratory tests can be used to assess haemostasis Laboratory testing Routine tests to determine normal haemostasis Specialised tests to determine the type of abnormality if an abnormality found in routine testing. All tests must have control plasma run with them − In many cases, the difference between patient and control that is more important than normal ranges Sample collection A clean venous blood sample for coagulation Blood should be immediately placed into plastic tubes containing appropriate anticoagulants: − potassium EDTA: full blood count − sodium citrate: clotting studies Blood should be gently mixed Blood should be tested ASAP (≤ 2-4 hrs) Preparation of PPP (platelet-poor plasma) Accurate coagulation testing requires the plasma free of platelets (except platelet function tests) Immediately spin the sample (3000rpm, 10 min) Keep the sample at room temperature until PPP obtained to prevent platelet activation Test immediately or remove the plasma and store (at 4oC for a few hours or - 40oC for several wks) Pre-analytical & analytical variation Common technical “errors” affect coagulation results Pre-analytical variation − Poor sample collection − Wrong anticoagulant / no anticoagulant − Contamination − Storage / transportation Analytical variation − Incorrect temperature for analysis − Out of date or poorly prepared reagents − Out of date or poorly prepared control material Tests of haemostatic function Routine tests Bleeding time: an index of platelet integrity Activated partial thromboplastin time (APTT): test for Intrinsic + Common (XII, XI, IX, VIII, X, V, II & I) Prothrombin time (PT): test for Extrinsic + Common (VII, X, V, II & I) Special Investigations 50:50 Correction Studies (APTT) − With normal plasma − With known deficient plasmas (which factor) Factor Assays (level of deficiency of that factor) Inhibitor Studies (abnormal inhibitor to coagulation) Disorders of Haemostasis I Normal haemostasis Major types of haemostatic disorders Abnormalities of blood platelets Disorders of blood coagulation Major types of haemostatic disorders Disorders of primary haemostasis Platelet abnormalities Defects of small blood vessels Skin and mucous membrane especially involved Disorders of blood coagulation Congenital clotting factor deficiency Acquired disorders of coagulation Typically: haemarthroses, muscle haematomas, bleeding after injury/surgery Disorders of Haemostasis I Normal haemostasis Major types of haemostatic disorders Abnormalities of blood platelets Disorders of blood coagulation Abnormalities of blood platelets Bleeding due to − Thrombocytopenia − Abnormal platelet function Characterised by purpura and bleeding from mucous membranes Symptoms related to platelet count − >80 x109/L - no clinical defect − < 50 x109/L- bleeding after trauma − < 20x109/L - spontaneous bleeding Thrombocytopenic purpura Causes of thrombocytopenia: Failure of production Increased destruction Sequestration Causes of thrombocytopenia - Failure of production Megaloblastic anaemia Haematological malignancy Solid tumour infiltration Aplastic anaemia/bone marrow failure Causes of thrombocytopenia - Increased destruction/use of platelets Autoimmune (ITP Idiopathic thrombocytopenic purpura ) Secondary immune (SLE, viruses, drugs) Alloimmune (neonatal & post-transfusion purpura) DIC (disseminated intravascular coagulation) Thrombotic thrombocytopenic purpura Causes of thrombocytopenia - Sequestration Hypersplenism Liver Spleen Idiopathic thrombocytopenic purpura (ITP) Bleeding disorder due to immune destruction of platelets Causes & pathogenesis: Immune system produces platelet Ab → Ab attach to platelets→ spleen destruction ITP in children: usually acute but self-limiting; bone marrow examination not usual ITP in adult: less acute than in children; characteristically in women; associated with other autoimmune disorders (e.g. SLE); platelets Ab in 60-70% patients ITP Clinical features: − Major haemorrhage rare, seen only with severe thrombocytopenia − Easy bruising, purpura, epistaxis, menorrhagia − Physical examination: normal except evidence of bleeding Laboratory investigation: − Thrombocytopenia: the only blood count abnormality − Anti-platelet auto-antibodies ITP Treatment In children, not usually require treatment; if necessary: − High dose anti-inflammatory steroid. − i.v. immunoglobin (very serious bleeding, urgent surgery) In adults − Platelets ≥30x109/L - no treatment − First line: corticosteroids (iv IgG if rapid platelets rise desired) − Second line: splenectomy (majority respond), if fails other treatments (high dose corticosteroids, immunosuppresion; recombinant thrombopoietin). − Platelet transfusion (intracranial or other extreme haemorrhage) Disorders of Haemostasis Normal haemostasis Major types of haemostatic disorders Abnormalities of blood platelets Disorders of blood coagulation Disorders of blood coagulation Coagulation/fibrinolytic disorders may cause thrombosis or haemorrhage Congenital or acquired Majority of these are acquired Congenital coagulation disorder Uncommon and usually involve deficiency of one factor only Deficiencies of all factors have been described Clinically most important: − Haemophilia A − Haemophilia B − Von Willebrand’s disease Haemophilia A Haemophilia A (classic haemophilia) – inherited as X-linked, recessive trait; 1 per 10,000 population Occurring mainly in males Deficiency of factor VIII (FVIII) Clinical features of Haemophilia A Clinical severity depends on residual FVIII activity − < 1%, bleeding spontaneously − 1-5%, bleeding after minor trauma − >5%, asymptomatic Coagulation deficiency type bleeding; purpura is not a feature - spontaneous bleeding into muscle, joints; bleeding after dental surgery typical Aids is a major complication in some patients (due to treatment with FVIII concentrate) Haemophilia A: Laboratory feature & treatment Laboratory feature: − Partial thromboplastin time prolonged; FVIII ↓ (