Disorders of coagulation

11.3 Disorders of coagulation



Evelyn Doyle




Essentials



1 Haemophilia and von Willebrand disease account for the majority of inherited coagulation disorders.

2 A positive family history of a bleeding disorder should be sought when a coagulation disorder is suspected.

3 Establishing disease severity (assayed factor levels), past history of bleeding, the nature of this bleed and presence of inhibitors will help guide replacement therapy in haemophilia.

4 Always consider ‘hidden’ potentially life-threatening bleeding: intracranial bleeding is a major cause of mortality in the haemophiliac patient.


Haemophilia



Introduction


Haemophilia A and B are coagulation disorders usually transmitted by X-linked recessive inheritance (70% of cases) but can occur as spontaneous gene mutations (30% of cases). Haemophilia A results from factor VIII deficiency and Haemophilia B (Christmas disease) is caused by factor IX deficiency. Acquired haemophilia is rare and occurs when autoantibodies develop against factor VIII.



Clinical presentation


Haemophilia A and B are clinically indistinguishable. Disease severity correlates well with assayed factor levels: severe disease occurs with factor levels <1% of normal, moderate and mild disease occur with levels between 1–5% and above 5%, respectively. In the absence of a positive family history, disease may go undetected for a variable period, depending on disease severity, with some cases of mild disease being diagnosed in adulthood.


Bleeding can occur in any tissue and may occur spontaneously or with minimal trauma. Most neonates, even those with severe disease, are born without significant bleeding, though intracranial haemorrhage may occur. As a child starts to ambulate bleeding episodes becomes more frequent. Unlike disorders of platelet function where mucosal bleeding typically occurs, bleeding into joints and soft tissues is characteristic, with large joints of the knee, ankle, hip, elbow, wrist and shoulder involved most frequently.


Other significant and potentially life-threatening bleeding can occur and should be considered in the haemophiliac patient: intracranial haemorrhage occurs with increased frequency after head trauma, retroperitoneal haematoma may occur spontaneously or following trauma and may mimic appendicitis, soft tissue haemorrhage in the head or neck is potentially life threatening due to the risk of airway obstruction. Gastrointestinal haemorrhage is a less common manifestation of haemophilia in children. Haematuria may be macroscopic or microscopic.


In the current paediatric haemophiliac population, transfusion-borne viruses including hepatitis B and C and human immunodeficiency virus are rare, as most cases of transmission occurred prior to 1985.



Investigations


Haemophilia A and B both cause a prolonged activated partial thromboplastin time (aPTT) with a normal prothrombin time and platelet count. Individual factor assays can then be performed to confirm the diagnosis. Haemophiliacs presenting with suspected intracranial or retroperitoneal bleeds need computerised tomography (CT) scanning. Plain radiographs will exclude fractures associated with traumatic haemarthroses.



Treatment


The primary treatment goal is control of bleeding by replacement of clotting factor. Factor concentrates are available as virus-inactivated plasma-derived product and recombinant factor concentrates. When available and expense allows, recombinant factor concentrates should be used. Factor replacement may be given following a confirmed bleed or as prophylaxis against potential bleeding; for example, prior to dental extraction. Prophylactic factor replacement, usually given two to three times a week at home, with increased doses given for any breakthrough bleeds, has led to a marked reduction in the number and severity of bleeding episodes.


The half-life of factor VIII is 8–12 hours and factor XI is up to 24 hours, so repeated doses may be needed. Many patients now initiate treatment for minor bleeds at home. Early and appropriate treatment reduces the risk of deterioration to disabling arthropathy and chronic pain. The amount of clotting factor required depends on the patient’s weight, severity of disease, the location of the bleed and also previous bleeding in the same area and presence of inhibitors


Lacerations generally require factor replacement to prevent excessive bleeding. Head injury requires a high index of suspicion and a very low threshold for factor treatment. Continuous intravenous (IV) factor infusion may be required for major bleeding. A negative cranial CT scan does not preclude the need for factor replacement.


Analgesia should be provided as required but aspirin should be avoided. Other non-steroidal anti-inflammatory drugs may be used on the advice of the treating haematologist. Narcotic analgesia has limitations associated with use in treating a chronic condition.


Desmopressin (DDAVP), a synthetic analogue of vasopressin that elevates factor VIII levels for several hours after administration by stimulating release from endothelial stores, can be used to treat mild haemophilia A. In an emergency situation where no clotting factor is available, fresh frozen plasma (FFP) or cryoprecipitate can be administered.


Inhibitors are alloantibodies that develop against clotting factors and are present in 10–20% of those with haemophilia A and 3–5% of those with haemophilia B. Inhibitors may mean that large amounts of clotting factor are required, or that clotting factors will not work at all. Treatment options for patients with haemophilia are prothrombin complex concentrate (prothrombinex) or recombinant activated factor VIIa. Elimination of inhibitors is possible in a proportion of patients using immune tolerance therapy, where daily low-dose factor infusions will lead to the development of neutralising anti-inhibitor antibodies.

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Sep 7, 2016 | Posted by in EMERGENCY MEDICINE | Comments Off on Disorders of coagulation

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