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Rare bleeding disorders


BSS, 325, 2%


FXIII, 1054, 6%


GT, 1884, 10%


F1, 1196, 7%


FV, 1420, 8%


FV + VIII, 385, 2%


WFH global survey 2011 F11, 244, 1%


FXI, 4759, 27%


FVII, 5357, 30%


FX, 1317, 7%


6000 5000 4000 3000 2000 1000 0


F1 Number of people FII FV + VIII FV FVII FX FXI FXIII GT BSS


Figure 1: Data from the World Federation of Haemophilia survey 2011 (http://www1.wfh.org/publications/files/pdf-1488.pdf ) showing the distribution of the rare disorders and their absolute number reported from a total of 108 countries (with permission from the World Federation of Haemophilia (www.wfh.org). BSS =Bernard-Soulier syndrome; GT = Glanzmann thrombasthenia.


of a bleeding disorder. When a girl presents to hospital at menarche with excessive bleeding or develops iron deficiency anaemia, she should be investigated for a bleeding disorder.


Single factor deficiencies (Fibrinogen, Factor II (Prothrombin), Factor V (FV), Factor VII (FVII), Factor X (FX), Factor XIII (FXIII).1


)


All the rare coagulation disorders are autosomally inherited, so there is no sex bias, unlike haemophilia A and B, which are carried on the X-chromosome and so manifest principally in males. These disorders are very rare, ranging from 1 in 2 million for FXIII deficiency to 1 in 500,000 for FVII deficiency. These broad figures are somewhat misleading, however, as these disorders are most common in racial groups and regions where consanguineous marriage is practised, for example, those of Asian and Far Eastern origin. Figure 1 shows data collected by the 2011 Annual Global Survey across the world by the World Federation of Haemophilia (WFH). The absolute numbers of some disorders, such as factor II deficiency, are very small. Table 1 shows the numbers collected by the WFH in successive years in comparison to haemophilia and von Willebrand disease. If the factor is completely absent, the bleeding risk is high. Infants born with severe deficiencies of any of these factors are at risk of intracranial haemorrhage in the first week of life. It is important that clinicians recognise abnormal bleeding and instigate urgent investigation because early


treatment can be life saving and/or prevent major disability. Excessive bleeding from the umbilical cord may occur particularly in fibrinogen or factor XIII deficiency. Other unusual bleeding may occur, such as from the gastrointestinal tract. Lesser degrees of deficiency are generally associated with less severe symptoms and later presentation, but there is not always a good correlation between measured factor and bleeding risk. Although these disorders are usually described as autosomal recessive, this implies that the parents are carriers without symptoms. Recent studies have identified mild bleeding symptoms in some carriers and these disorders (particularly FVII and FX) should not be assumed to be recessive. Recent studies have demonstrated that the traditional classification of these disorders into mild, moderate and severe using the criteria for haemophilia A and B is not applicable to these disorders.2


Diagnosis is made by appropriate coagulation screening tests with factor assays, and should be done in association with a haematologist, preferably one experienced in haemostasis. It should be noted that all screening tests are normal in FXIII deficiency, so that, if suspected, a FXIII level needs to be measured. Other bleeding manifestations are variable and none are specific to any one disorder. Symptoms include mucous membrane bleeding (excessive or abnormal epistaxis, menorrhagia), easy bruising, muscle and joint bleeding (FV and FVII deficiencies). Women are


particularly likely to experience menstrual problems, which can include ovarian haemorrhage presenting as acute abdominal pain. This may be overlooked as the bleeding is internal, but it may be life threatening. Women with bleeding disorders are also susceptible to excessive bleeding during childbirth.3


In addition to the general measures described above, specific factor replacement may be required for prevention or treatment of bleeding. Some individuals with severe bleeding will require prophylaxis, for example, a diagnosis of severe FXIII deficiency should be followed by introduction of prophylaxis with concentrate. Factor concentrates (combined or


single) are available for all these deficiencies (variable access in different countries), apart from FV deficiency which requires fresh frozen plasma, preferably pathogen inactivated (PI-FFP). Factor concentrates are often stored and issued within haemophilia centres or from transfusion laboratories rather than from pharmacy departments, but arrangements will vary.


Congenital platelet disorders These may present with very similar symptoms to those of the coagulation disorders, but mucous membrane bleeding and easy bruising are particular features.4


The most severe forms of


platelet disorder will be diagnosed in infancy but investigation of platelet number and function is an important part of the diagnostic work up for the


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