Hereditary haemorrhagic telangiectasia is a rare disorder with autosomal dominant inheritance. Mutations occur in genes that encode components of the TGF-beta signaling pathway that is involved in blood vessel development. Dilation of capillaries and small arterioles produces characteristic small red spots that blanch on pressure in the skin and mucous membranes.
Easy bruising syndrome is a common benign disorder occurring in otherwise healthy women. It is characterized by bruises on the arms, legs, trunk with minor trauma, possibly because of skin vessel fragility.
Senile purpura and purpura due to steroids are both due to atrophy of vascular supporting tissue.
Henoch-Schonlein purpura is a type III hypersensitivity (immune complex) reaction that is often preceded by an acute upper respiratory tract infection
PLATELET DISORDERS
Thrombocytopenia
Thrombocytopenia is caused by reduced platelet production in the bone marrow, excessive peripheral destruction of platelets or sequestration in an enlarged spleen. Specific tests may be useful to confirm the presence of conditions such as paroxysmal nocturnal haemoglobinuria (PNH) or systemic lupus erythematous (SLE). Treating underlying disease is enough by high risk bleeding platelet transfusion is indicated.
Immune thrombocytopenia Purpura
Thrombocytopenia is due to immune destruction of platelets. The antibodies found have specificity for platelet membrane glycoprotein IIb/IIA and/or Ib.
ITP in children occurs most commonly in age group 2-6 years. IPS has an acute onset with mucocutaneous bleeding and there may be a history of recent viral infection, including varicella zoster or measles.
ITP in adults. The presentation is usually less acute than in children. ITP is characteristically seen in women and maybe associated with other autoimmune disorders such as SLE, thyroid disease and autoimmune haemolytic anaemia (Evans' syndrome). It is also seen in CLL and HIV.
Clinical features. Easy bruising, purpura, epistaxis and menorrhagia are common. Physical examination is normal except for evidence of bleeding
Investigation. The only count abnormalities is thrombocytopenia. Normal or increased numbers of megakaryocytes are found in bone marrow.
Treatment
Children usually don't require treatment. Where this is necessary, corticosteroids, intravenous immunoglobulin and anti-D are effective.
Adults with platelets count >30x10^9/L generally require no treatment unless they are about to undergo a surgical procedure. First-line therapy consists of oral corticosteroids. Intravenous immunoglobulin is effective. Second-line therapy involves splenectomy, to which the majority of patients respond. Third-line therapy includes high dose corticosteroid, intravenous immunoglobulin, anti-D, vinca alkaloids, danazol, immunosuppressive agents, combination chemotherapy and mycophenolate mofetil.
Thrombotic thrombocytopenia purpura (TTP)
TTP arises due to endothelial damage and microvascular thrombosis. This occurs due to a reduction in ADAMTS-13 a protease which is normally responsible for regulating the size of von Willebrand factor (vWF) Reduction in ADAMTS-13 results in multiorgan microthrombi. In congenital cases the the deficiency is due to mutations in the ADAMTS-13 gene. Secondary causes of acute TTP include pregnancy, oral contraceptives, SLE, infection and drug treatment.
Treatment consists of plasma exchange, it provides a source of ADAMTS-13. Pulsed intravenous methylprednisolone is given acutely as is increasingly rituximab as a primary treatment of choice. Disease activity is monitored by measuring the platelet count and serum LDH.
Platelet function disorders
Platelet function disorders are usually associated with excessive bruising and bleeding and in some of the acquired forms, with thrombosis. The platelet count is normal or increased and the bleeding time is prolonged.
Thrombocytosis
The platelet count may rise above 400x10^9/L as a result of:
- Splenectomy
- Malignant disease
- Inflammatory disorders such as rheumatoid arthritis and inflammatory bowel disease
- Major surgery and post haemorrhage
- Myeloproliferative disorders
- Iron deficiency
Essential thrombocythaemia. Myeloproliferative disorder and other myeloproliferative conditions such as polythemia vera (PV), myelofibrosis and chronic myeloid leukaemia (CML) may also be associated with high platelet count.
A persistently elevated platelet count can lead to arterial or venous thrombosis
INHERITED COAGULATION DISORDERS
Haemophilia A is due to a lack of factor VIII. It is inherited as an X-linked disorder. Bleeding is treated by administration of factor VIII concentrate by intravenous infusion to achieve normalization of levels. Factor VIII has a half-life of 12h and therefore must be administered at least twice a daily. Complications. Up to 30% of people with severe haemophilia will, during their lifetime, develop antibodies to factor VIII that inhibit its action. Such inhibitors usually develop after the first few treatment doses of factor VIII. Recombinant factor VIIa at very high 'pharmacological' levels can bypass factor IX/VIII activity and is an effective treatment in more than 80% of bleeding episodes in patients with high levels of inhibitor antibodies. The long-term aim of management is to eradicate the inhibitory antibody. This is done using immune tolerance induction strategies, sometimes using additional immunosuppression and immunoabsorption.
Haemophilia B (Christmas disease)
Haemiphilia B is caused by a deficiency of factor IX. The inheritance and clinical features are identical to haemophilia A. It is treated with factor IX concentrate and prophylactic doses given twice a day.
Von Willebrand's Disease (VWD)
In WVD there is defective platelets function as well as factor VIII deficiency and both are due to a deficiency or abnormality of vWF. vWF plays a role in platelet adhesion to damaged subendothelium as well as stabilizing factor VIII in plasma.
ACQUIRED COAGULATION DISORDERS
Vitamin K deficiency
Vitamin K is necessary for carboxylation of glutamic acid residues on coagulation factors II, VII, IX, X and on proteins C and S. Without it these factors cannot bind calcium.
Deficiency of vitamin K may be due to:
- Inadequate stores e.g. malnutrition
- Malabsorption of vitamin K
- Oral anticoagulant drugs which are vitamin K antagonists
Liver disease
Liver disease may result in a number of defects in haemostasis:
- Vitamin K deficiency - intrahepatic or extrahepatic cholestasis.
- Reduced systhesis. Reduced synthesis of coagulation factors c\may be result of severe hepatocellular damage.
- Thrombocytopenia - hypersplenism due to splenomegaly associated with portal hypertension or from folic acid deficiency
- Disseminated intravascular coagulation occurs in acute liver failure.
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