Trombositopenia dan Trombositosis

Definisi

Gangguan myeloproliferatif kronik :

gangguan akibat abnormalitas clonal hematopoetic stem cell yg didapat (akuisita), mengakibatkan peningkatan selularitas sum2 tulang yg diikuti peningkatan jumlah sel darah perifer termasuk trombositosis

_______________________________________ Hematopoetic stem cell : sel primitif sum2 tulang, asal dari seluruh jenis sel darah Clonal/Monoclonal : propagasi sel yang berasal dari sel progenitor tunggal

Classification of myeloproliferative disorders.

Myeloproliferative syndromes Polycythemia vera Myelofibrosis Essential thrombocytosis Chronic myeloid leukemia Myelodysplastic syndromes Acute myeloid leukemia

Polisitemia Vera
Essentials of Diagnosis Increased red blood cell mass. Splenomegaly. Normal arterial oxygen saturation. Usually elevated white blood count and platelet count.

Causes of polycythemia. Spurious polycythemia Primary polycythemia : PV Secondary polycythemia 1. Hypoxia: cardiac disease, pulmonary disease, high altitude 2. Carboxyhemoglobin: smoking 3. Renal lesions 4. Erythropoietin-secreting tumors (rare)

The hematocrit > 54% (M) or 51% in (F) When the hematocrit is elevated, the red blood cell mass should be measured to determine whether true polycythemia or relative (Spurius) polycythemia exists. True polisitemia ( elevated Red Cell Mass): primary or secondary. Primary polycythemia (polycythemia vera) is a bone marrow disorder characterized by autonomous overproduction of erythroid cells. The serum erythropoietin level is low. In vitro, erythroid progenitor cells grow without added erythropoietin, a finding not seen in normal individuals.

Secondary polycythemia 1. Hypoxia: cardiac disease, pulmonary disease, high altitude 2. Carboxyhemoglobin: smoking 3. Renal lesions 4.Erythropoietin-secreting tumors (rare) Relative ("spurious") polycythemia presents in overweight and hypertensive (often on diuretic therapy); Hmt <60%, normal red cell mass and low-plasma volume.

Sign and simptom

Symptoms related to expanded blood volume and increased blood viscosity. Common complaints: headache, dizziness, tinnitus, blurred vision, and fatigue. Generalized pruritus,and epistaxis. 60% are men, and the median age at presentation is 60 years. Polycythemia rarely occurs in persons under age 40 years. Physical examination: reveals plethora and engorged retinal veins. Spleenomegaly in 75% of cases but is nearly always enlarged when imaged Thrombosis is the most common complication of polycythemia vera and the major cause of morbidity and death. There is a high incidence of peptic ulcer disease.

Laboratory Finding

Hematocrit above normal, at times greater than 60%. Red blood cell morphology is normal. The red blood cell mass is elevated. The white blood count is elevated to 10,000-20,000/uL The platelet count is variably increased, sometimes to counts exceeding 1,000,000/uL. Platelet morphology is usually normal. The bone marrow is hypercellular, with panhyperplasia Iron stores are usually absent from the bone marrow Overproduction of uric acid may lead to hyperuricemia. Microcytosis, hypochromia, and poikilocytosis may result from iron deficiency Progressive hypersplenism may also lead to elliptocytosis.

Differensial Diagnosis
Laboratory features of myeloproliferative disorders.

WhiteCount Hematocrit Platelet Count Red cellMorphology Chronic myeloid leukemia I N N or I N Myelofibrosis N or D or I N or I D or N or I Abn Polycythemia vera N or I I N or I N Essential thrombocytosis N or I N I N

Treatment

Phlebotomy. One unit of blood (approximately 500 mL) weekly target: less than 45%. Myelosuppressive therapy : a high phlebotomy requirement, thrombocytosis, and intractable pruritus. Hydroxyurea >> Alkylating because of less leukemogenic potential. The usual dose is 500-1500 mg/d orally Target: platelets < 500,000/uL and neutrophil count < 2000/uL. Anagrelide is a new drug for trombositosis Low-dose aspirin (81-325 mg daily) has been shown to reduce the risk of thrombosis.

Prognosis

Polycythemia is an indolent disease with median survival of 11-15 years. The major cause of morbidity and mortality is arterial thrombosis. Polycythemia vera may convert to myelofibrosis or to chronic myelogenous leukemia. In approximately 5% of cases, the disorder progresses to acute myelogenous leukemia, which is usually refractory to therapy.

Essential Trombositosis
Essentials of Diagnosis Elevated platelet count in absence of other causes. Normal red blood cell mass. Absence of Philadelphia chromosome.

Symptoms and Signs

Median age: 50-60 years, slightly increased incidence in women. Finding of an elevated platelet count. First sign is thrombosis. Venous thromboses may occur in unusual sites such as the mesenteric, hepatic, or portal vein. Some patients experience erythromelalgia(painful burning and erythema) Bleeding Splenomegaly is present in at least 25% of patients.

Laboratory Findings

Elevated platelet count is the hallmark of this disorder, and may be over 2,000,000/uL. WBC mildly elevated (not above 30,000/uL), but with some immature myeloid forms. The hematocrit is normal. The peripheral blood smear reveals large platelets, but giant degranulated forms seen in myelofibrosis are not observed. Red blood cell morphology is normal. The bleeding time is prolonged in 20% of patients. The bone marrow : increased megakaryocytes but no other morphologic abnormalities. The Philadelphia chromosome is absent to differentiate from chronic myeloid leukemia.

Differensial Diagnosis
Laboratory features of myeloproliferative disorders.

WhiteCount Hematocrit Platelet Count Red cellMorphology Chronic myeloid leukemia I N N or I N Myelofibrosis N or D or I N or I D or N or I Abn Polycythemia vera N or I I N or I N Essential thrombocytosis N or I N I N

Treatment

Standard therapy has consisted of hydroxyurea in a dose of 0.5-2 g/d. Anagrelide is highly effective in a dose of 2-4 mg/d but may cause headache, mild anemia, and peripheral edema, and in high doses congestive heart failure. Vasomotor symptoms such as erythromelalgia and paresthesias respond rapidly to aspirin and eventually to control of the platelet count. Plateletpheresis.

Prognosis

Essential thrombocytosis is an indolent disorder Average survival is longer than 15 years from diagnosis The major source of morbidity thrombosis can be reduced by appropriate platelet control. The bone marrow may become fibrotic, and massive splenomegaly may occur, sometimes with splenic infarction. There is a 10-15% risk of progression to myelofibrosis after 15 years, and a 1-5% risk of transformation to acute leukemia over 20 year

IDIOPATHIC (AUTOIMMUNE) THROMBOCYTOPENIC PURPURA Essentials of Diagnosis Isolated thrombocytopenia. Other hematopoietic cell lines normal. No systemic illness. Spleen not palpable. Normal bone marrow with normal or increased megakaryocytes.

Patophysiology

ITP: autoimmune disorder in which an IgG autoantibody is formed that binds to platelets. Platelets are not destroyed by direct lysis. Destruction takes place in the spleen, where splenic macrophages with Fc receptors bind to antibody-coated platelets. Splenectomy is highly effective therapy.

Symptoms and Signs

ITP commonly in childhood Precipitated by viral infection and usually self-limited. Adult form is usually a chronic disease and only infrequently follows a viral infection. Incidence between ages 20 and 50 years, and there is a 2:1 female predominance. Presenting complaint is mucosal or skin bleeding (epistaxis, oral bleeding, menorrhagia, purpura, and petechiae). An enlarged spleen should lead one to doubt the diagnosis.

Laboratory Findings

The hallmark of the disease is thrombocytopenia, with platelet counts that may be less than 10,000/uL. Other counts are usually normal except for occasional mild anemia, which can be explained by bleeding or associated hemolysis (Evans's syndrome). Peripheral blood cell morphology is normal except that platelets are slightly enlarged (megathrombocytes). The bone marrow will appear normal, with a normal or increased number of megakaryocytes. Coagulation studies will be entirely normal.

Differensial Diagnosis
Causes of thrombocytopenia. Bone marrow disorders 1. Aplastic anemia 2. Hematologic malignancies 3. Myelodysplasia 4. Megaloblastic anemia 5. Chronic alcoholism Nonmarrow disorders 1. Immune disorders 2. Idiopathic thrombocytopenic purpura 3. Drug-induced 4. Secondary (CLL, SLE)1 5. Posttransfusion purpura 6. Hypersplenism 7. Disseminated intravascular coagulation 8. Thrombotic thrombocytopenic purpura 9. Hemolytic-uremic syndrome 10. Sepsis 11. Hemangiomas 12. Viral infections, AIDS 13. Liver failure 14. 1CLL = chronic lymphocytic leukemia; SLE = systemic lupus erythematosus.

Treatment

Initial treatment is with prednisone, 1-2 mg/kg/d. Prednisone works primarily by decreasing the affinity of splenic macrophages, reduces the binding of antibody to the platelet surface, decrease antibody production, enhanced vascular stability. the risk of bleeding is small with platelet counts above 50,000/uL. An alternative steroid regimen is the use of high-dose dexamethasone, 40 mg/d for 4 days. Splenectomy is the most definitive treatment for idiopathic thrombocytopenic purpura, Splenectomy is indicated if patients do not respond to prednisone. Splenectomy can be performed safely even with platelet counts less than 10,000/uL. CR 80%

Treatment

High-dose intravenous immunoglobulin, 1 g/kg for 1 or 2 days, is highly effective in rapidly raising the platelet count. Use for bleeding emergencies or situations. Danazol, vincristine, azathioprine, cyclosporine, and cyclophosphamide. Rituximab can produce good responses in some patients with refractory disease. Platelet transfusions are rarely used in the treatment of idiopathic thrombocytopenic purpura,

Prognosis

The prognosis for remission is good. The major concern during the initial phases is cerebral hemorrhage, which becomes a risk when the platelet count is less than 5000/uL. Very low platelet counts caused fatal bleeding is rare.

THROMBOTIC THROMBOCYTOPENIC PURPURA

Essentials of Diagnosis Thrombocytopenia. Microangiopathic hemolytic anemia. Neurologic and renal abnormalities, fever. Reduced level of ADAMTS13. Normal coagulation tests. Elevated serum LDH.

Introducing

TTP is an uncommon syndrome with microangiopathic hemolytic anemia, thrombocytopenia, and a markedly elevated serum LDH. Deficiency of a von Willebrand factor-cleaving protease, ADAMTS13, to platelet agglutination and adhesion to endothelium. TTP is seen primarily in young adults between ages 20 and 50 years, female predominance. The syndrome is occasionally precipitated by estrogen use, pregnancy, drugs, or infections. The most common drugs implicated are quinine and ticlopidine. The syndrome may also occur as a complication of bone marrow transplantation or the use of cyclosporine or tacrolimus. Familial cases occur, but are rare.

Symptoms and Signs

Anemia, bleeding, or neurologic abnormalities. Neurologic symptoms include headache, confusion, aphasia, and alterations in consciousness from lethargy to coma. With more advanced disease, hemiparesis and seizures may occur.
On examination, the patient appears acutely ill and is usually febrile. Pallor, purpura, petechiae, and signs of neurologic dysfunction may be detected. Patients may have abdominal pain and tenderness due to pancreatitis. Differential Diagnosis The normal values of coagulation tests differentiate TTP from DIC. Other conditions causing microangiopathic hemolysis (Table 13-18) should be excluded. Evans's syndrome is the combination of autoimmune thrombocytopenia and autoimmune hemol

Laboratory Findings

Anemia Reticulocytosis and circulating nucleated red blood cells. The hallmark is a microangiopathic blood picture with fragmented red blood cells Thrombocytopenia is invariably present and may be severe. Increasing indirect bilirubin LDH is markedly elevated in proportion to the severity of hemolysis; Coombs test is negative. Coagulation tests (prothrombin time, partial thromboplastin time, fibrinogen) are normal unless ischemic tissue damage causes secondary disseminated intravascular coagulation (DIC) present elevated fibrin degradation products may be seen. ADAMTS13 is usually absent during active disease. Pathologically, there may be thrombi in capillaries and small arteries, with no evidence of inflammation.

Differensial Diagnosis

Evans's syndrome is the combination of autoimmune thrombocytopenia and autoimmune hemolytic anemia, but the peripheral smear will show spherocytes and not red blood cell fragments. TTP and hemolytic-uremic syndrome are not distinct disease entities, TTP characterized by more neurologic and severe thrombocytopenia and hemolytic-uremic syndrome with more renal failure.

Treatment

Plasmapheresis. 60 to 80 mL/kg of plasma should be removed and replaced with fresh-frozen plasma. Treatment should be continued daily until the patient is in complete remission. Prednisone and antiplatelet agents (aspirin [325 mg three times daily] and dipyridamole [75 mg three times daily]) The combination of splenectomy, corticosteroids, and dextran has been used with success. Splenectomy performed in remission may prevent subsequent relapses. Immunosuppression with drugs such as cyclophosphamide has also been effective.

Prognosis

With plasmapheresis, 80 to 90 percent of patients now recover completely. Neurologic abnormalities are almost always completely reversed. Most complete responses are durable, but in 20% of cases the disease will be chronic and relapsing.