Bleeding Disorders: Causes and Diagnosis

Bleeding Disorders

• Bleeding can be due to congenital or acquired abnormalities in the clotting system.
• History and examination help to clarify the severity and the underlying cause of the bleeding problem.

Patterns of Bleeding

• Mucosal bleeding:
  • Reduced number or function of platelets (e.g. bone marrow failure or aspirin)
  • Deficiency of von Willebrand factor (e.g. von Willebrand disease)
  • Characterized by:
    • Skin: petechiae, bruises
    • Gum and mucous membrane bleeding
    • Fundal haemorrhage
    • Post-surgical bleeding
• Coagulation factor deficiency (e.g. haemophilia or warfarin/anticoagulant):
  • Bleeding into joints (haemarthrosis) or muscles
  • Bleeding into soft tissues
  • Retroperitoneal haemorrhage
  • Intracranial haemorrhage
  • Post-surgical bleeding

Normal Haemostasis

• Stage 1: Pre-injury conditions encourage flow
• Stage 2: Early haemostatic response: platelets adhere; coagulation is activated
• Stage 3: Fibrin clot formation
• Stage 4: Limiting clot formation: natural anticoagulants reverse activation of coagulation factors
• Stage 5: Fibrinolysis: plasmin degrades fibrin to allow vessel recanalisation and tissue repair

Pathological Bleeding

• Normal bleeding is seen following surgery and trauma
• Pathological bleeding occurs when structurally abnormal vessels rupture or when a vessel is breached in the presence of a defect in haemostasis
• May be due to a deficiency or dysfunction of platelets, the coagulation factors, or von Willebrand factor, or occasionally to excessive fibrinolysis

Clinical Assessment

• A careful clinical evaluation is the key to diagnosis of bleeding disorders
• Consider the following:
  • Site of bleeding
  • Duration of history: congenital or acquired
  • Precipitating causes: spontaneous indicates a more severe defect
  • Surgery
  • Family history
  • Drugs history
  • Site of bleeding

Causes of Bleeding Disorders

• Disorders of primary haemostasis:
  • Vessel wall abnormalities (e.g. hereditary haemorrhagic telangiectasia, vasculitis, or scurvy)
  • Platelet function disorders (e.g. Glanzmann's thrombasthenia, Bernard-Soulier syndrome)
• Thrombocytopenia:
  • Occurs in many disease processes
  • Can be immune-mediated or due to increased consumption or inhibition of function of coagulation factors
• Disorders of secondary haemostasis (coagulation):
  • Haemophilia A (factor VIII deficiency)
  • Haemophilia B (factor IX deficiency)

Haemophilia A

• Factor VIII deficiency resulting in haemophilia A affects 1/10,000 individuals
• Sex-linked disorder located on the X chromosome
• Factor VIII is primarily synthesised by the liver and endothelial cells and has a half-life of about 12 hours

Management of Haemophilia

• Bleeding in mild and moderate forms usually do not require specific treatment, just supportive treatment
• Severe forms require treatment with factor VIII or IX concentrates or cryoprecipitate

Von Willebrand Disease

• Common but usually mild bleeding disorder caused by a quantitative or qualitative deficiency of von Willebrand factor (vWF)
• vWF is synthesised by endothelial cells and megakaryocytes, and is involved in both platelet function and coagulation

Management of Von Willebrand Disease

• Many episodes of mild haemorrhage can be successfully treated by local means or with desmopressin, which raises the vWF level, resulting in a secondary increase in factor VIII
• Tranexamic acid may be useful in mucosal bleeding
• For more serious or persistent bleeds, haemostasis can be achieved with selected factor VIII concentrates, which contain considerable quantities of vWF in addition to factor VIII

Thrombotic Disorders

Venous Thromboembolic Disease

• Most common presentations: deep vein thrombosis (DVT) of the leg and/or pulmonary embolism
• Management:
  • Anticoagulation with low-molecular-weight heparin (LMWH) followed by a coumarin anticoagulant, such as warfarin
  • Alternatively, direct oral anticoagulants (DOACs) can be used immediately from diagnosis without the need for LMWH

Disseminated Intravascular Coagulation (DIC)

• Complicates a range of illnesses
• Characterised by systemic activation of the pathways involved in coagulation and its regulation
• May result in the generation of intravascular fibrin clots causing multi-organ failure, with simultaneous coagulation factor and platelet consumption, causing bleeding

Management of DIC

• Therapy is primarily aimed at the underlying cause
• Often require intensive care to deal with concomitant issues, such as acidosis, dehydration, renal failure, and hypoxia