Therapeutic principles The extent of haemorrhage depends on the severity of the factor VIII or IX deficiency and the severity of the trauma. Therapy consists of temporarily raising the concentration of the deficient factor, appropriate supportive measures, analgesia and graded physiotherapy. In minor trauma in mild haemophilia A, infusions of a synthetic vasopressin analogue (desmopressin, DDAVP; Chapter 36), produce a short-term two- to four-fold increase in factor VIII. Fluid overload due to the antidiuretic hormone action of DDAVP must be prevented by limiting water intake. DDAVP is usually given with an inhibitor of fibrinolysis, such as tranexamic acid. If the haemophilia and/or trauma is severe, then infusions of factor VIII or IX are required. Patients and their parents or other carers are taught to administer these factors at home in order to minimize delay in therapy. FACTOR VIII Factor VIII used to be obtained from purified pooled plasma of blood donors, but recombinant preparations are free of potential viral pathogens, including hepatitis B, hepatitis C, HIV and cytomegalovirus (CMV). It is given as an intravenous infusion. It is highly bound to von Willebrand factor (�95%) and is degraded by reticuloendothelial cells in the liver. The dose of factor VIII is calculated on the basis of the severity of the injury and the required increase in plasma factor VIII concentration. Transient reactions to infusions (e.g. urticaria, flushing and headache) occur, but respond to antihistamines. Anaphylactic reactions are rare. FACTOR IX Factor IX is used in patients with factor IX deficiency. It acts as a cofactor for factor VIII and as recombinant factor IX is available for patients with haemophilia B the recombinant form does not contain other factors or potential pathogens. Factor IX is given as an intravenous infusion. The use and adverse effects of factor IX are similar to those described for factor VIII. FACTOR VIIA Recombinant activated factor VII (rFVIIa) is a haemostatic protein. It was originally developed to treat bleeding episodes in haemophilic patients with inhibitors against coagulation factors VIII and IX. It is used by specialists to achieve haemostasis in several severe congenital and acquired haemorrhagic states. Key points Coagulation factor therapy • Factor VIII is used to treat haemophilia A (factor IX is used for haemophilia B) when patients present with severe bleeding. • These factors are given intravenously and the dose is based on the level of factor deficiency and blood loss. • Recombinant coagulation factors are free from the risk of contamination with infectious agents, such as HIV and hepatitis C, and cause less antibody production. IDIOPATHIC THROMBOCYTOPENIC PURPURA 395 APLASTIC ANAEMIA Aplastic anaemia is characterized by pancytopenia associated with absence of haematological precurors in the marrow. Some cases are congenital (e.g. Fanconi’s anaemia), but many are acquired, and in 50% of these an aetiological agent (a virus, chemical or drug) can be implicated. Certain drugs predictably cause aplastic anaemia if given in sufficient dose (e.g. alkylating agents, such as cyclophosphamide), others (e.g. chloramphenicol) may cause aplastic anaemia as an idiosyncratic type B adverse reaction (Chapter 12). TREATMENT Support is provided with transfusions (of red cells and platelets) and appropriate antibiotics. Successful bone marrow transplantation is curative and is the therapy of choice for young patients. For those who are unsuitable for this treatment, or in cases where there is no available histocompatible donor, anabolic steroids, e.g. oxymetholone or stanozolol and epoetin and G-CSF (see above) may reduce the requirement for transfusions. IDIOPATHIC THROMBOCYTOPENIC PURPURA It is important to exclude other causes of thrombocytopenia, including drugs (e.g. quinine). Platelet transfusions are required to control active bleeding or to cover operations. Other treatment options include: • glucocorticosteroids – e.g. prednisolone: an increase in platelet count may take one to two weeks. If steroids fail or the disease relapses, splenectomy should be considered. The patient should be immunized against pneumococcal infection several weeks preoperatively. Glucocorticosteroids should be continued after splenectomy until the platelet count rises. • immunosuppressive drugs (Chapters 48 and 50), especially vincristine, are used in refractory cases. • intravenous immunoglobulin (IVIG), rituximab, anti-CD20 antibody (Chapter 50) and ciclosporin are alternatives. Key points Drug-related haematological toxicity • Cytotoxic cancer chemotherapy can suppress all haematopoietic lineages. • Drugs that cause aplastic anaemia include ticlopidine, indometacin, carbimazole and zidovudine. • Drugs that cause agranulocytosis include, for example, carbamazepine, propylthiouracil, NSAIDs, H2 antagonists and antipsychotics (e.g. chlorpromazine, clozapine). • Drugs that cause thrombocytopenia include, for example, heparin, azathioprine, quinidine and thiazides. • Drugs that cause haemolytic anaemia include, for example, methyldopa, β-lactams (penicillins and cephalosporins).
396 ANAEMIA AND OTHER HAEMATOLOGICAL DISORDERS Case history A 65-year-old woman presents to the medical out-patient department with a history of fatigue. She has in the last few months been undergoing adjuvant cytotoxic chemotherapy for a node-positive resected breast cancer. The patient is pale, but no other abnormalities are noted. Her full blood count shows a haemoglobin level of 9.8 g/dL with a mean corpuscular volume of 86 fL; other haematological indices and serum transferrin are normal. Her faecal occult blood is negative. She is started on oral iron sulphate and given weekly injections of erythropoietin 40 000 U subcutaneously. Three months later, her haemoglobin level has risen to 13.5 g/dL, but she presents to the Accident and Emergency Department with acute-onset dysphasia and weakness of her right arm. Her supine blood pressure is 198/122 mmHg. Her neurological deficit resolves over 24 hours and her blood pressure settles to 170/96 mmHg. She has no evidence of cardiac dyshythmias or of carotid disease on ultrasonic duplex angiography, and her serum cholesterol concentration was 4.2 mmol/L. Question What led to this patient’s acute neurological episode? Does she require further therapy? Answer Her mild normochromic-normocytic anaemia was most likely related to her cytotoxic cancer therapy. Treatment with iron and erythropoietin was indicated. She was not iron deficient, and using iron and erythropoietin in combination for a haemoglobin �10 g/dL is well justified. The most common dose-limiting side effects of erythropoietic drug administration are hypertension and thrombosis, which are implicated in the left middle cerebral transient ischaemic attack (TIA) she has suffered. Treatment with erythropoietin and iron should be stopped, and her blood pressure monitored over 8–12 weeks. If hypertension is solely related to the erythropoietin therapy, her blood pressure should normalize and no further treatment will be required. In retrospect it may have been prudent to have more closely monitored her erythropoietic therapy and once her Hb �12 g/dL stopped it as this may have avoided her neurological event. FURTHER READING Akkerman JW. Thrombopoietin and platelet function. Seminars in Thrombosis and Hemostasis 2006; 32: 295–304. Chong BH, Ho SJ. Autoimmune thrombocytopenia. Journal of Thrombosis and Haemostasis 2005; 3: 1763–72. Franchini M. Recombinant factor VIIa: a review on its clinical use. International Journal of Hematology 2006; 83: 126–38. Kaushansky K. Lineage-specific hematopoietic growth factors. New England Journal of Medicine 2006; 354: 2034–45. Limentani SA, Roth DA, Furie BC, Furie B. Recombinant blood clotting proteins for haemophilia therapy. Seminars in Thrombosis and Hemostasis 1993; 19: 62–7. McGrath K. Treatment of anaemia caused by iron, vitamin B 12 or folate deficiency. Medical Journal of Australia 1989; 157: 693–7. Scott J, Weir D. Folate/vitamin B 12 inter-relationships. Essays in Biochemistry 1994; 28: 63–72. Umbreit J. Iron deficiency: a concise review. American Journal of Hematology 2005; 78: 225–31.
Soliman s Auricular Therapy Textbook: New Localizations and Evidence Based Therapeutic Approaches was created ( M.D. Nader Soliman )
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Soliman s Auricular Therapy Textbook This textbook is considered the finest ever written in the field of auricular therapy. The auricular acupuncture microsystem is one of the most widely used special acupuncture techniques. This textbook is dedicated to teaching the sound foundations of this unique approach as introduced by its founder Dr. Paul Nogier of France. The scientific bases of the acupuncture microsystem with its three dime... Full description
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