Myeloproliferative disorders

Patients in the more aggressive categories are less likely to exhibit involvement of the skin and have a less favorable prognosis [10]. Those patients may have a definable hematological disorder such as a myelodysplastic syndrome, myeloproliferative disorder, acute leukemia, or a malignant lymphoma. In aggressive mastocytosis and mast cell leukemia, the clinical course is determined by the rapidity of the increase in mast cell numbers. 

Recommended levels WBC greater than or equal to 3,500/mm1 2 3 and ANC greater than or equal to 2,000/mm3 No history of a myeloproliferative disorder... 

Hydroxyurea is an older agent still used occasionally today for patients with psoriasis however, there have been recent precautions about its use in the elderly and cutaneous vasculitic toxicities in patients with myeloproliferative disorders.29 Toxicity associated with tacrolimus has limited its use in psoriasis. Azathioprine has a slow onset and significant toxicity.29 Oral corticosteroids are reserved for severe or life-threatening conditions such as severe psoriatic arthritis or exfoliative psoriasis prolonged oral steroid use should be avoided.10... 

Cancers Multiple myeloma Non-Hodgkin s lymphoma Hodgkin s disease Acute myeloid leukemia Neuroblastoma Germ cell tumors Acute myeloid leukemia Acute lymphoblastic leukemia Chronic myeloid leukemia Myelodysplastic syndrome Myeloproliferative disorders Non-Hodgkin s lymphoma Hodgkin s disease Chronic lymphocytic leukemia Multiple myeloma... 

Myeloproliferative disorder A group of diseases of the bone marrow in which excess cells, usually lymphocytes, are produced. Myelosuppression A condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets. Myelosuppression is a side effect of some cancer treatments. Myocardial contractility The force of contraction of the heart during systole. 

Since HU needs to be taken lifelong in the treatment of non-neoplastic conditions such as SCA (since the inhibition of ribonucleotide reductase is reversible) a major concern is its long term secondary effects. Several studies have shown the potential leukomegenic effect of HU in myeloproliferative disorders [22], [23]. Such concern becomes quite legitimate in sickle cell patients with permanently expanded erythropoiesis in whom the use of HU is at the limit of marrow toxicity. Hence alternative therapies must be sought for. 

Allopurinol is the antihyperuricemic drug of choice in patients with a history of urinary stones or impaired renal function, in patients who have lymphoproliferative or myeloproliferative disorders and need pretreatment with a xanthine oxidase inhibitor before initiation of cytotoxic therapy to protect against acute uric acid nephropathy, and in patients with gout who are overproducers of uric acid. 

Wandl, U.B. et al., Lupus-like autoimmune disease induced by interferon therapy for myeloproliferative disorders, Clin. Immunol. Immunopathol., 65, 70, 1992. 

Thrombocythemia For the treatment of patients with thrombocythemia, secondary to myeloproliferative disorders, to reduce the elevated platelet count and the risk of thrombosis and to ameliorate associated symptoms including thrombo-hemorrhagic events. 

Children Myeloproliferative disorders are uncommon in pediatric patients and limited data are available in this population. 

Clozapine Myeloproliferative disorders uncontrolled epilepsy history of clozapine-induced agranulocytosis or severe granulocytopenia should not be used with other agents having a well-known potential to cause agranulocytosis or suppress bone marrow function. 

Its primary indications are myeloproliferative disorders, including chronic granulocytic leukemia, polycythemia vera, and essential thrombocytosis. It is also used in combination with radiotherapy for head and neck cancer and for carcinoma of the cervix. Hydroxycarbamide is well absorbed after oral administration. It is in part metabolized in the liver and also excreted unchanged in the urine its elimination half-life is 2-5 hours. Its major toxicity consists of short lasting bone marrow depression. 

Hydroxyurea. - Hydroxyurea, H2NC(0)NH0H, is used in the treatment sickle cell disease and myeloproliferative disorders. The interaction of HU with Hb-Fe(Il)-02 results in the production of Hb-Fe(II)-NO, Hb-Fe(III) and NOu. The anti-proliferative action of HU results from its inhibition of ribonucleotide reducase (a key enzyme in DNA synthesis), which is believed to involve the reaction of NO with a tyrosyl radical formed during the reaction cycle. King et... 

Kamiyama, R. (1982). Fibrous long spacing-like fibers in the bone marrow of myeloproliferative disorder. Virchows Arch. B Cell Pathol. Incl. Mol. Pathol. 39, 285-291. 

Folic acid deficiency, unlike vitamin B12 deficiency, is often caused by inadequate dietary intake of folates. Alcoholics and patients with liver disease develop folic acid deficiency because of poor diet and diminished hepatic storage of folates. There is also evidence that alcohol and liver disease interfere with absorption and metabolism of folates. Pregnant women and patients with hemolytic anemia have increased folate requirements and may become folic acid-deficient, especially if their diets are marginal. Evidence implicates maternal folic acid deficiency in the occurrence of fetal neural tube defects, eg, spina bifida. (See Folic Acid Supplementation A Public Health Dilemma.) Patients with malabsorption syndromes also frequently develop folic acid deficiency. Folic acid deficiency is occasionally associated with cancer, leukemia, myeloproliferative disorders, certain chronic skin disorders, and other chronic debilitating diseases. Patients who require renal dialysis also develop folic acid deficiency, because folates are removed from the plasma each time the patient is dialyzed. 

Platelet counts above 400,000/pil are referred to as thrombocytosis, Thrombocytosis is classified as being either primary or secondary, Primary thrombocytosis or essential thrombo-cythemia is associated with chronic myeloproliferative disorders such as chronic myeloid leukemia, polycythemia vera, and agnogenic myeloid metaplasia. Exclusion-based diagnosis of essential thrombocythemia is made when patients... 

Hepatic venous thrombosis, also known as Budd-Chiari syndrome, is caused by hypercoagulable disorders precipitated by pregnancy, infection, and birth control medication. An acute painful abdomen, sudden enlargement of the liver, and the presence of ascites make up a triad of clinical symptoms that are important in the diagnosis of this syndrome. Myeloproliferative disorders such as polycythemia vera and paroxysmal nocturnal dyspnea were previously thought to be responsible. Factor V Leiden and prothrombin 20210 mutations are also known to be responsible, Other intraabdominal thromboses include portal vein thrombosis, mesenteric vein thrombosis and renal vein thrombosis. 

Elevated white blood cells and a predominance of neutrophils is consistent with a bacterial infection, although other possible causes include steroid administration, myeloproliferative disorders, inflammation (e.g. vasculitis) and acute haemorrhage. 

Polycythemia is usually defined as a hematocrit above 0.50 in males and 0.47 in females. Polycythemia rubra vera or primary polycythemia, a myeloproliferative disorder, may be complicated by TIAs, ischemic stroke or intracranial venous thrombosis (Silverstein et at 1962 Pearson and Wetherley-Mein 1978 Markus and Hambley 1998). Ischemic complications may occur because the platelet count is raised and platelet activity enhanced, or... 

Essential thrombocythemia, or idiopathic primary thrombocytosis, is another myeloproliferative disorder in which the platelet count is raised, usually to over 1000 x lO cells/1. Secondary thrombocytosis occurs in malignancy, splenectomy, hyposplenism, surgery, trauma, hemorrhage, iron deficiency, infections, polycythemia rubra vera, myelofibrosis and the leukemias. There is a tendency for arterial and venous thrombosis and, paradoxically, intracranial hemorrhage because the platelets are hemostatically defective (ArboLx et al. 1995 Harrison et al 1998 Mosso et al. 2004 Ogata et al 2005). 

Braun, B.S., et al. (2004). Somatic activation of oncogenic Kras in hematopoietic cells initiates a rapidly fatal myeloproliferative disorder. Proc Natl Acad Sci USA 101 597-602. 

We described a patient with a bleeding disorder, whose platelets were completely deficient in GPIa and intact thr< nbospondin and did not aggregate in resprmse to collagen . Acquired deficiencies of the platelet GPIa/IIa ccmplex with absoice of responsiveness of the platelets to collagens due to myeloproliferative disorders have been described . ... 

Viero P, Cortdaza> S, Barbui T, Gaetano G. Defective platdd aggregation induced by platdd activating factor in myeloproliferative disorders deficiency of an a irin-independent mechanism. Haemostasis 1986 16 27-33... 

Allopurinol is indicated in recurrent gout, when at least three attacks occur per year, in blood diseases where there is spontaneous hyperuiicaemia, and during treatment of myeloproliferative disorders where cell destruction creates a high urate load. Allopurinol prevents the hyperuricaemia due to diuretics and may be combined with a uricosuric agent. The dose is usually 300 mg/d by mouth but some patients may need as much as 600 mg daily. 

Dubois, A., Dauzat, M., Pignodel, Cb., Pomier-Layrargues, G., Marty-Double, Ch., Lopez, F.-M., Janbon, C. Portal hypertension in lympho-proliferative and myeloproliferative disorders hemodynamic and histological correlations. Hepatology 1993 17 246-250... 

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