Classification of bleeding disorders
- Bleeding disorders can arise from disorders of the:
- Vessel wall
- Platelets
- Coagulation system
Vessel wall
- Hereditary haemorrhagic telangiectasia
- Ehlers-Danlos syndrome
- Drugs (e.g. steroids)
- Sepsis
- Trauma
- Vasculitis
Platelets
- Congenital platelet disorders
- Thrombocytopenia
- Myeloproliferative disorders
- Drugs (e.g. aspirin)
Coagulation system
- Haemophilia A, B
- Von Willebrand disease
- Factor IX, XIII deficiency
- Liver disease
- Anticoagulants
- Disseminated intravascular coagulation
Coagulation tests
Prothrombin time (PT)
- Tests extrinsic and common pathways
- Thromboplastin and calcium are added to patient plasma
- PT is expressed as ration (International Normalised Ratio = INR)
- Prolonged in:
- Warfarin treatment
- Liver disease
- Vitamin K deficiency
- Disseminated intravascular coagulation
Activated partial thromboplastin time (APPT, KCCT)
- Tests intrinsic and common pathways
- Kaolin added to patient plasma
- Prolonged in:
- Heparin treatment
- Haemophilia and factor deficiencies
- Liver disease
- Disseminated intravascular coagulation
- Massive transfusion
- Lupus anticoagulant
Thrombin time (TT)
- Tests common pathway
- Thrombin added to patient plasma
- Converts fibrinogen into fibrin
- Prolonged in:
- Heparin treatment
- Disseminated intravascular coagulation
- Dysfibrinogenaemia
Bleeding time (BT)
- Measures capillary bleeding
- Prolonged in:
- Platelet disorders
- Vessel wall disorders
Haemophilia
- Haemophilia A is due to factor VIII deficiency
- Haemophilia B (Christmas disease) is due to factor IX deficiency
Haemophilia A
- Affects about 1 in 10,000 population
- It is a sex-linked clotting disorder
- One-third of patients have no family history
- Usually presents in childhood with:
- Prolonged haemorrhage after dental extraction
- Recurrent haemarthroses or muscle haematomas
- Sub-periosteal haematomas can result in haemophilic pseudo-tumours
- Clinical severity depends on extent clotting factor deficiency
- <1% activity - severe disease with life-threatening bleeding
- 1-5% activity - moderate disease with post-traumatic bleeding
- 5-20% activity - mild disease
Investigation
- Activated partial thromboplastin time (APPT) is prolonged
- prothrombin time (PT) is normal
- Whole blood coagulation time is prolonged
- Factor VIII is reduced
Treatment
- Bleeding episodes are treated with factor VIII replacement
- Given as either factor VIII concentrate or cryoprecipitate
- Bleeding usually well controlled if factor VIII levels raised above
20% normal
- Desmopressin increases intrinsic factor VIII levels
- 5-10% develop antibodies to factor VIII
- Renders patients refractory to factor replacement therapy
Disseminated intravascular coagulation
- Due to widespread intravascular activation of clotting cascade
- Causes a bleeding tendency due to consumption of clotting factors
- Presents with bruising or purpura
- Oozing from surgical wounds and venepuncture sites
Causes
- Severe (usually gram-negative or meningococcal) infection
- Widespread mucin-secreting metastatic adenocarcinoma
- Hypovolaemic shock
- Burns
- Transfusion reactions
- Eclampsia
- Amniotic fluid embolus
- Promyelocytic leukaemia
Investigation
- Increased KPPT and PT
- Reduced serum fibrinogen levels (<1 mg / ml)
- Thrombocytopenia
- Increased fibrin degradation products
- Factor V and VIII activities are reduced
Treatment
- Fluid resuscitation
- Treat underlying cause
- Correct clotting abnormalities with:
- Fresh frozen plasma
- Cryoprecipitate
- Platelet transfusion
Recombinant Factor VIIa
- Factor VIIa is a trypsin-like serine protease
- Its is an initiator of thrombin generation
- Acts via two pathways to activate Factor Xa
- One pathway is at the site of tissue injury complexed with Tissue
Factor
- The other pathway is on the platelet surface independent of Tissue
Factor
- Tissue factor is found in the subendothelial layer of the vascular
wall
- Not normally available to complex with Factor VIIa
- Following injury subendothelial layer is exposed and tissue factor
can bind to Factor VIIIa
- Theoretically both mechanisms localises action of Factor VIIa to the
site of trauma
Clinical uses
- Licensed for use in haemophiliacs with antibodies to Factor VIII
- May have use in trauma patients with massive blood loss
- Reduces visible coagulopathic haemorrhage
- Significantly reduces blood transfusion requirements in patients
with blunt trauma
- May also reduce incidence of MOF and ARDS in trauma patients
Bibliography
Bolton-Maggs P H B, Pasi K J. Haemophilias A
and B. Lancet 2003; 361: 1801-1809
Ludlam C A.
Treatment of haemophilia.
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101 (Suppl 1):
13-14.
Richard P, Dutton M D, McCunn M et
al. Factor VIIa for the correction of traumatic coagulopathy.
J Trauma 2004; 57: 709-719.
Senno S L,
Pechet L, Bick R L. Disseminated intravascular coagulopathy (DIC):
pathophysiology, laboratory diagnosis and management.
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