Apakah penyakit thalassemia itu?
Thalassemia adalah penyakit keturunan dengan gejala utama pucat, perut tampak membesar karena pembengkakakan limpa dan hati, dan apabila tidak diobati dengan baik akan terjadi perubahan bentuk tulang muka dan warna kulit menjadi menghitam. Penyebab penyakit ini adalah kekurangan salah satu zat pembentuk hemoglobin (Hb) sehingga produksi hemoglobin berkurang.
Apakah hemoglobin itu?
Hemoglobin adalah suatu zat di dalam sel darah merah yang berfungsi mengangkut zat asam dari paru-paru ke seluruh tubuh, selain itu yang memberikan warna merah sel darah merah. Hemoglobin terdiri dari 4 molekul zat besi (heme), 2 molekul rantai globin alpha dan 2 molekul rantai globin beta. Rantai globin alpha dan beta adalah protein yang produksinya disandi oleh gen globin alpha dan beta.
Apakah gel globin alpha dan gen globin beta?
Setiap sifat dan fungsi fisik pada tubuh kita dikontrol oleh gen yang bekerja sejak masa embrio. Gen terdapat di dalam sel tubuh kita. Setiap gen selalu berpasangan. SAtu belah gen berasal dari ibu dan yang lainnya dari ayah. Di antara banyak gen dalam tubuh kita, terdapat sepasang gen yang mengontrol pembentukan hmogelon pada setiap sel darah merah. Gen tersebut dinamakan gen globin. Gen – gen tersebut terdapat di dalam kromosom.
Bagaimana terjadinya penyakit thalassemia?
Penyakti thalassemia disebabkan oleh adanya kelainan / perubahan / mutasi pada gen globin alpha atau gen globin beta sehingga produksi rantai globin tersebut berkurang dan sel darah merah mudah sekali rusak atau umurnya lebih pendek dari sel darah normal (120 hari). Bila kelainan pada gen globin alpha maka penyakitnya disebut thalassemia alpha, sedangkan kelainan pada gen globin beta akan menyebabkan penyakit thalassemia beta. Karena di Indonesia thalassemia beta lebih sering didapat, maka selanjutnya kami hanya akan menjelaskan mengenai thalassemia beta.
Bagaimana cara penurunannya?
Penyakit ini diturunkan melalui gen yang disebut sebagai gen globin beta yang terletak pada kromosom 11. Pada manusia kromosom selalu ditemukan berpasangan. Gen globin beta ini yang mengatur pembentukan salah satu komponen pembentuk hemoglobin. Bila hanya sebelah gen globin beta yang mengalami kelainan disebut pembawa sifat thalassemia beta. Seorang pembawa sifat thalassemia tampak normal / sehat, sebab masih mempunyai 1 belah gen dalam keadaan normal (dapat berfungsi dengan baik). Seorang pembawa sifat thalassemia jarang memerlukan pengobatan. Bila kelainan gen globin terjadi pada kedua kromosom, dinamakan penderita thalassemia (homosigot / Mayor). Kedua belah gen yang sakit tersebut berasal dari kedua orang tua yang masing-masing membawa sifat thalassemia.
Pada proses pembuahan, anak hanya mendapat sebelah gen globin beta dari ibunya dan sebelah lagi dari ayahnya. Bila kedua orang tuanya masing-masing pembawa sifat thalassemia maka pada setiap pembuahan akan terdapat beberapa kemungkinan. Kemungkinan pertama si anak mendapat gen globin yang berubah (gen thalassemia) dari bapak dan ibunya, maka anak akan menderita thalassemia. Sedangkan bila anak hanya mendapat sebelah gen thalassemia dari ibu atau ayah, maka anak hanya membawa penyakit ini. Kemungkinan lalin adalah anak mendapatkan gen globin normal dari kedua orang tuanya.
Bagaimana terjadinya gejala pucat atau anemia?
Warna merah dari darah manusia disebabkan oleh hemoglobin yang terdapat di dalam sel darah merah. Hemoglobin terdiri atas zat besi dan protein yang dibentuk oleh rantai globin alpha dan rantai globin beta. Pada penderita thalassemia beta, produksi rantai globin beta tidak ada tau berkurang. Sehingga hemoglon yang dibentuk berkurang. Selain itu berkurangnya rantai globin beta mengakitbatkan rantai globin alfa berlebihan dan akan saling mengikat membentuk suatu benda yang emnyebabkan sel darah merah mudah rusak. Berkurangnya produksi hemoglobin dan mudah rusaknya sel darah merah mengakibatkan penderita menjadi pucat atau anemia atau kadar Hbnya rendah.
Mengapa limpa membesar pada penderita thalassemia?
Limpa berfungsi membersihkan sel darah merah yang sudah rusak. Selain itu limpa juga berfungsi membentuk sel darah pada masa janin. Pada penderita thalassemia, sel darah merah yang rusak sangat berlebihan sehingga kerja limpa sangat berat. Akibatnya limpa menjadi membengkak. Selain itu, tugas limpa lebih diperberat untuk memproduksi sel darah emrah lebih banyak.
Mengapa terjadi perubahan bentuk tulang muka?
Sumsum tulang pipih adalah tempat memproduksi sel darah. Tulang muka adalah salah satu tulang pipih. Pada thalassemia karena tubuh kekurangan darah, maka pabrik sel darah, dalam hal ini sumsum tulang pipih, akan berusa memproduksi sel darah merah sebanyak-banyaknya. Karena pekerjaannya yang meningkat, maka sumsum tulang ini akan membesar, pada tulang muka pembesaran ini dapat dilihat dengan jelas dengan adanya penonjolan dahi, jarak antara kedua mata menjadi jauh, kedua tulang pipi menonjol.
Apakah pengobatan penyakit thalassemia?
Sampai saat ini belum ada obat yang menyembuhkan penyakit thalssemia secara total. Pengobatan yang paling optimal adalah transfusi darah seumur hidup dan mempertahankan kadar Hb selalu sama atau 12 g/dl dan mengatasi akibat samping transfusi darah.
Apakah efek samping transfusi darah?
Efek samping transfusi darah adalah kelebihan zat besi dan terkena penyakit yang ditularkan melalui darah yang ditransfusikan. Setiap 250 ml darah yang ditransfusikan selalu membawa kira-kira 250 mg zat besi. Sedangkan kebutuhan normal manusia akan zat besi hanya 1 – 2 mg per hari. Pada penderita yang sudah sering mendapatkan transfusi kelebihan zat besi ini akan ditumpuk di jaringan-jaringan tubuh seperti hati, jantung, paru, otak, kulit dan lain-lain. Penumpukan zat besi ini akan mengganggu fungsi organ tubuh tersebut dan bahkan dapat menyebabkan kematian akibat kegagalan fungsi jantung atau hati.
Bagaimana mengatasi kelebihan zat besi?
Pemberian obat kelasi besi atau pengikat zat besi (nama dagangnya Desferal) secara teratur dan terus-menerus akan mengatasi masalah kelebihan zat besi. Obat kelasi besi (Desferal) yang saat ini tersedia di pasaran diberikan melalui jarum kecil ke bawah kulit (subkutan) dan obatnya dipompakan secara perlahan-lahan oleh alat yang disebut “syringe driver.” Pemakaian alat ini diperlukan karena kerja obat ini hanya efektif bila diberikan secara perlahan-lahan selama kurang lebih 10 jam per hari. Idealnya obat ini diberikan lima hari dalam seminggu seumur hidup.
source : http://www.phtdi.org/content/view/15/
websidenya PHTDI (Perhimpunan Hematologi dan Transfusi Darah Indonesia)
Tampilkan postingan dengan label Hematology. Tampilkan semua postingan
Tampilkan postingan dengan label Hematology. Tampilkan semua postingan
Kamis, 01 Juli 2010
Selasa, 04 Mei 2010
Bleeding Disorders : Therapy
a. Thrombocytopenia caused by drugs
- Discontinue use of possible offending agents, except recovery in 7-10 days. Platelet transfusions may be needed if platelet count on < style="font-weight: bold;">b. Heparin-Induced Thrombocytopenia
- Discontinue heparin promptly.
- A direct thrombin inhibitor such as lepirudin (0,4-mg/kg bolus, 0,15-mg/kg per hour infusion, PTT target 1,5-2,5 x baseline) should be used for treatment of thromboses.
- Do not use low-molecular-weight heparin (LWMH), as antibodies often cross react.
c. Chronic ITP
- Prednison, initially 1-2 mg/kg per day, then slow taper to keep the platelet count > 60.000/µL.
- IV immunoglobulin (2 g/kg in devided doses oveeer 2-5 days) to block phagocytic destruction may be useful.
- Rituximab is effective in patients refractory to glucocorticoids.
- Splenectomy, danazol (androgen) or other agents (e.g., vincristine, cyclophosphamide, fludarabine) are indicated for refractory patients or those requiring >5-10 mg prednisone daily.
d. DIC
- Control of underlying disease most important, platelets, fresh frozen plasma (FFP) to correct clotting parameters.
- Heparin may be beneficial in patients with acute promyelocytic leukemia.
e. TTP
- Plasmapheresis and FFP infusions (plasma exchange), possibly IV IgG, recovery in two-thirds of cases.
- Plasmapheresis removes inhibitors of the vWF cleavage enzyme (ADAMTS13), and FFP replaces the enzyme.
f. Disorders of Platelet Function
- Remove or reverse underying cause
- Dialysis and/or cryoprecipitate infusions (10 bags/24h) may be helpful for platelet dysfunction associated with uremia
g. Hemostatic Disorders
- Withdraw offending drugs, replace vitamin C, plasmapheresis, and plasma infusion for TTP.
h. Hemophilia A
- Factor VIII replacement for bleeding or befor surgical procedure, degree and duration of replacement depends on severity of bleeding.
- Give factor VIII (e.g. Recombinate) to obtain a 15% (for mild bleeding) to 50% (for severe bleeding) factor VIII level.
- The duration should range from a single dose of factor VIII to therapy bid for up to 2 weeks. Dose is calculated as follows
Factor VIII dose + (target level-baseline level) x weight (kg) x 0,5 unit/kg.
i. Hemophilia B
- Recombinant factor IX (e.g Benefix), FFP or factor IX concentrates (e.g., Proplex, Konyne).
- Because of the longer half-life, once daily treatment is sufficient.
- Dose is calculated as follows :
Factor IX dose = (Target level-baseline level) x weight (kg) x1 unit/kg
j. Von Willebrand Disease
- Desmopresin (1-deamino-8-D arginine vasopressin increases release of vWF from endothelial stores in type 1 vWD.
- It is given IV (0,3 µg/kg) or by nasal spray (2 squirts of 1,5 mg/mL luid in each nostril).
- For types 2A, 2M, and 3, cryoprecipitate (plasma product rich in factor VIII) or factor VIII concentrate (Humate-P, Koate HS) is used up to 10 bags bid 72 h, depending on severity of bleeding.
k. Vitamin K deficiency
- Vitamin K, 10 mg SC or slow IV
l. Liver Disease
- Fresh-frozen plasma
17th Edition Harrison’s Manual of Medicine, 2009 Chap. 68. Bleeding and Thrombotic Disorders p. 332
For more detailed, see
Konkle BA : Bleeding and Thrombosis, Chap 59, p.363
Konkle BA : Disorders of platelets and Vessel Wall, chap 109, p. 718
Arruda V, High KA : Coagulation Disorders, chap 110, p.725
Weititz JI : Antiplatelet, Anticoagulant, and Fibrionolytic Drugs, chap 112, p. 735, in HPIM-17
- Discontinue use of possible offending agents, except recovery in 7-10 days. Platelet transfusions may be needed if platelet count on < style="font-weight: bold;">b. Heparin-Induced Thrombocytopenia
- Discontinue heparin promptly.
- A direct thrombin inhibitor such as lepirudin (0,4-mg/kg bolus, 0,15-mg/kg per hour infusion, PTT target 1,5-2,5 x baseline) should be used for treatment of thromboses.
- Do not use low-molecular-weight heparin (LWMH), as antibodies often cross react.
c. Chronic ITP
- Prednison, initially 1-2 mg/kg per day, then slow taper to keep the platelet count > 60.000/µL.
- IV immunoglobulin (2 g/kg in devided doses oveeer 2-5 days) to block phagocytic destruction may be useful.
- Rituximab is effective in patients refractory to glucocorticoids.
- Splenectomy, danazol (androgen) or other agents (e.g., vincristine, cyclophosphamide, fludarabine) are indicated for refractory patients or those requiring >5-10 mg prednisone daily.
d. DIC
- Control of underlying disease most important, platelets, fresh frozen plasma (FFP) to correct clotting parameters.
- Heparin may be beneficial in patients with acute promyelocytic leukemia.
e. TTP
- Plasmapheresis and FFP infusions (plasma exchange), possibly IV IgG, recovery in two-thirds of cases.
- Plasmapheresis removes inhibitors of the vWF cleavage enzyme (ADAMTS13), and FFP replaces the enzyme.
f. Disorders of Platelet Function
- Remove or reverse underying cause
- Dialysis and/or cryoprecipitate infusions (10 bags/24h) may be helpful for platelet dysfunction associated with uremia
g. Hemostatic Disorders
- Withdraw offending drugs, replace vitamin C, plasmapheresis, and plasma infusion for TTP.
h. Hemophilia A
- Factor VIII replacement for bleeding or befor surgical procedure, degree and duration of replacement depends on severity of bleeding.
- Give factor VIII (e.g. Recombinate) to obtain a 15% (for mild bleeding) to 50% (for severe bleeding) factor VIII level.
- The duration should range from a single dose of factor VIII to therapy bid for up to 2 weeks. Dose is calculated as follows
Factor VIII dose + (target level-baseline level) x weight (kg) x 0,5 unit/kg.
i. Hemophilia B
- Recombinant factor IX (e.g Benefix), FFP or factor IX concentrates (e.g., Proplex, Konyne).
- Because of the longer half-life, once daily treatment is sufficient.
- Dose is calculated as follows :
Factor IX dose = (Target level-baseline level) x weight (kg) x1 unit/kg
j. Von Willebrand Disease
- Desmopresin (1-deamino-8-D arginine vasopressin increases release of vWF from endothelial stores in type 1 vWD.
- It is given IV (0,3 µg/kg) or by nasal spray (2 squirts of 1,5 mg/mL luid in each nostril).
- For types 2A, 2M, and 3, cryoprecipitate (plasma product rich in factor VIII) or factor VIII concentrate (Humate-P, Koate HS) is used up to 10 bags bid 72 h, depending on severity of bleeding.
k. Vitamin K deficiency
- Vitamin K, 10 mg SC or slow IV
l. Liver Disease
- Fresh-frozen plasma
17th Edition Harrison’s Manual of Medicine, 2009 Chap. 68. Bleeding and Thrombotic Disorders p. 332
For more detailed, see
Konkle BA : Bleeding and Thrombosis, Chap 59, p.363
Konkle BA : Disorders of platelets and Vessel Wall, chap 109, p. 718
Arruda V, High KA : Coagulation Disorders, chap 110, p.725
Weititz JI : Antiplatelet, Anticoagulant, and Fibrionolytic Drugs, chap 112, p. 735, in HPIM-17
Bleeding Disorders
Bleeding may result from abnormalities of
1. Platelets
2. Blood vessel walls
3. Coagulation.
Platelets disorders characteristically produce petechial and purpuric skin lesions and bleeding from mucosal surfaces. Defective coagulation results in ecchymoses, hematomas, and muscosal and, in some disorders, recurrent joint bleeding (hemarthroses).
Platelet Disorders
Thrombocytopenia.
Normal platelet count is 150.000-350.000/µL. Bleeding time, a measurement of platelet function, is abnormally increased if platelet count < 100.000/µL, injury or surgery may provoke excess bleeding. Spontaneous bleeding is unsual unless count < 20.000/µL, platelet count < 10.000/µL is often associated with serious hemorrhage. Bone marrow examination shows increased number of megakaryocytes in disorders associated with accelerated platelet destruction, decreased number in disorders of platelet production.
Causes
1. Production defects such as marrow injury (e.g. drugs, radiation), marrow failure (e.g., aplastic anemia), marrow invasion (e.g., carcinoma, leukemia, fibrosis).
2. Sequestration due to splenomegaly.
3. Accelerated destruction- causes include :
a. Drugs such as chemotherapeutic agents, thiazides, ethanol, estrogens, sulfonamides, quinidine, quinine, methyldopa.
b. Heparin-induced thrombocytopenic is seen in 5% of patients receiving >5 days of therapy and is due to in vivo platelet aggregation often from anti-platelet factor 4 antibodies. Arterial and occasionally venous thromboses may result.
c. Autoimmune destruction by an antibody mechanism, may be idiopathic or associated with systemic lupus erythematosus (SLE), lymphoma, HIV>
d. Idiopathic thrombocytopenic purpura (ITP) has two forms, an acute, self-limited disorder of childhood requiring no specific therapy, and a chronic disorder of adults (esp. woman 20-40 years). Chronic ITP may be due to autoantibodies to glycoprotein IIb-IIa or glycoprotein Ib-IX complexes.
e. Disseminated Intravascular Coagulation (DIC)-platelet consumption with coagulation factor depletion [prolonged prothrombin time (PT), partiaol thromboplastin time (PTT)] and stimulation of fibrinolysis [generation of fibrin split products (FSPs)}. Blood smear shows microangipathic hemolysis (schistocytes). Cause include infection (esp. meningococcal, pneumococcal, gram-negative bacteremias), extensive burns, trauma, or thrombosis, giant hemangioma, retained dead fetus, heat stroke, mismatched blood transfusion, metastatic carcinoma, acute promyelocytic leukemia.
f. Thormbotic thrombocytopenic purpura (TTP)-rare disorder characterized by microangipathic hemolytic anemia, fever, thrombocytopenia, renal dysfunction (and/or hematuria), and neurolofic dysfunction caused by failure to cleave von Willebrand factor (vWF) normally.
g. Hemorrhage with extensive transfusion.
Psudotheombocytopenia
Platelet clumping secondary to collection of blood in EDTA (0,3% of patients). Examination of blood smear establishes diagnosis.
Thrombocytosis
Platelet count >350.000/µL. Either primary (essential thrombocytosis) or secondary (reactive), later secondary to severe hemorrhage, iron deficiency, surgery, after splenectomy (transient), malignant neoplasms (esp. Hodgkin’s disease, polycythemia vera), chronic inflammatory disease (e.g. inflamatory bowel disease), recovery from acute infection, vitamin B12 deficiency, drugs (e.g., vincritistine, epinephrine). Rebound thrombocytosis may occur after marrow recovery from cytotoxic agents, alcohol. Primary thrombocytosis may be complicated by bleeding and /or thrombosis, secondary rarely causes hemostatic problems.
Disorders of Platelet Function
Suggested by the finding of prolonged bleeding time with normal platelet count. Defect is in platelet adhesion, aggregation, or granule release. Causes include :
1. Drugs-aspirin, other nonsteroidal anti-inflammatory drugs, dipyridamole, clopidogrel, heparin, penicillin, esp. carbenicillin,ticarcillin.
2. Uremia
3. Cirrhosis
4. Dysproteinemias
5. Myeloproliferative and myelodyplastic disorders
6. Von Willebrand disease
7. Cardiopulmonary bypass
Hemostatic Disorders Due to Blood Vessel Wall Defects
Causes include :
1. Aging
2. Drugs – e.g., glucocorticoid (chronic therapy), penicillins, sulfonamides.
3. Vitamin C deficiency
4. TTP
5. Hemolytic uremic syndrome
6. Henoch-Schonlein purpura
7. Paraproteinemias
8. Hereditary hemorrhagic telangiectasia (Osler-Rendu-Weber disease)
Disorders of Blood Coagulation
Congenital Disorders
1. Hemophilia A-incidence 1:5000, sex-linked recessive deficiency of factor VIII (low plasma factor VIII (low plasma factor VIII coagulant activity, but normal amount of factor VIII-related antigen-vWF). Laboratory features, elevated PTT, normal PT).
2. Hemophilia B (Christmas disease)-incidence 1:30.000, sex linked recessive, due to factor IX deficiency. Clinical and laboratory features similar to hemophilia A.
3. Von Willebrand disease-most common inherited coagulation disorder (1:800-1000), usually autosomal dominant, primary defect is reduced synthesis or chemically abnormal factor VIII-related antigen produced by platelets and endothelium, resulting in abnormal platelet function.
Acquired Disorders
1. Vitamin K deficiency-impairs production of factors II (prothrombin), VII, IX, and X, vitamin K is a cofactor in carboxylation of glutamate residues on prothrombin complex proteins, major source of vitamin K is dietary (esp. green vegetables), with minor production by gut bacteria. Laboratory features : elevated PT and PTT.
2. Liver disease – results in deficiencies of all clotting factor except VIII. Laboratory features : elevated PT, normal or elevated PTT.
3. Other disorders-DIC, fibrinogen deficiency (liver disease,L-asparaginase therapy, rattlesnake bites), other factor deficiencies, circulating anticoagulants (lymphoma, SLE, idiopathic), massive transfusion coagulopathy).
17th Edition Harrison’s Manual of Medicine, 2009 Chap. 68. Bleeding and Thrombotic Disorders p. 332
For more detailed, see
Konkle BA : Bleeding and Thrombosis, Chap 59, p.363
Konkle BA : Disorders of platelets and Vessel Wall, chap 109, p. 718
Arruda V, High KA : Coagulation Disorders, chap 110, p.725
Weititz JI : Antiplatelet, Anticoagulant, and Fibrionolytic Drugs, chap 112, p. 735, in HPIM-17
1. Platelets
2. Blood vessel walls
3. Coagulation.
Platelets disorders characteristically produce petechial and purpuric skin lesions and bleeding from mucosal surfaces. Defective coagulation results in ecchymoses, hematomas, and muscosal and, in some disorders, recurrent joint bleeding (hemarthroses).
Platelet Disorders
Thrombocytopenia.
Normal platelet count is 150.000-350.000/µL. Bleeding time, a measurement of platelet function, is abnormally increased if platelet count < 100.000/µL, injury or surgery may provoke excess bleeding. Spontaneous bleeding is unsual unless count < 20.000/µL, platelet count < 10.000/µL is often associated with serious hemorrhage. Bone marrow examination shows increased number of megakaryocytes in disorders associated with accelerated platelet destruction, decreased number in disorders of platelet production.
Causes
1. Production defects such as marrow injury (e.g. drugs, radiation), marrow failure (e.g., aplastic anemia), marrow invasion (e.g., carcinoma, leukemia, fibrosis).
2. Sequestration due to splenomegaly.
3. Accelerated destruction- causes include :
a. Drugs such as chemotherapeutic agents, thiazides, ethanol, estrogens, sulfonamides, quinidine, quinine, methyldopa.
b. Heparin-induced thrombocytopenic is seen in 5% of patients receiving >5 days of therapy and is due to in vivo platelet aggregation often from anti-platelet factor 4 antibodies. Arterial and occasionally venous thromboses may result.
c. Autoimmune destruction by an antibody mechanism, may be idiopathic or associated with systemic lupus erythematosus (SLE), lymphoma, HIV>
d. Idiopathic thrombocytopenic purpura (ITP) has two forms, an acute, self-limited disorder of childhood requiring no specific therapy, and a chronic disorder of adults (esp. woman 20-40 years). Chronic ITP may be due to autoantibodies to glycoprotein IIb-IIa or glycoprotein Ib-IX complexes.
e. Disseminated Intravascular Coagulation (DIC)-platelet consumption with coagulation factor depletion [prolonged prothrombin time (PT), partiaol thromboplastin time (PTT)] and stimulation of fibrinolysis [generation of fibrin split products (FSPs)}. Blood smear shows microangipathic hemolysis (schistocytes). Cause include infection (esp. meningococcal, pneumococcal, gram-negative bacteremias), extensive burns, trauma, or thrombosis, giant hemangioma, retained dead fetus, heat stroke, mismatched blood transfusion, metastatic carcinoma, acute promyelocytic leukemia.
f. Thormbotic thrombocytopenic purpura (TTP)-rare disorder characterized by microangipathic hemolytic anemia, fever, thrombocytopenia, renal dysfunction (and/or hematuria), and neurolofic dysfunction caused by failure to cleave von Willebrand factor (vWF) normally.
g. Hemorrhage with extensive transfusion.
Psudotheombocytopenia
Platelet clumping secondary to collection of blood in EDTA (0,3% of patients). Examination of blood smear establishes diagnosis.
Thrombocytosis
Platelet count >350.000/µL. Either primary (essential thrombocytosis) or secondary (reactive), later secondary to severe hemorrhage, iron deficiency, surgery, after splenectomy (transient), malignant neoplasms (esp. Hodgkin’s disease, polycythemia vera), chronic inflammatory disease (e.g. inflamatory bowel disease), recovery from acute infection, vitamin B12 deficiency, drugs (e.g., vincritistine, epinephrine). Rebound thrombocytosis may occur after marrow recovery from cytotoxic agents, alcohol. Primary thrombocytosis may be complicated by bleeding and /or thrombosis, secondary rarely causes hemostatic problems.
Disorders of Platelet Function
Suggested by the finding of prolonged bleeding time with normal platelet count. Defect is in platelet adhesion, aggregation, or granule release. Causes include :
1. Drugs-aspirin, other nonsteroidal anti-inflammatory drugs, dipyridamole, clopidogrel, heparin, penicillin, esp. carbenicillin,ticarcillin.
2. Uremia
3. Cirrhosis
4. Dysproteinemias
5. Myeloproliferative and myelodyplastic disorders
6. Von Willebrand disease
7. Cardiopulmonary bypass
Hemostatic Disorders Due to Blood Vessel Wall Defects
Causes include :
1. Aging
2. Drugs – e.g., glucocorticoid (chronic therapy), penicillins, sulfonamides.
3. Vitamin C deficiency
4. TTP
5. Hemolytic uremic syndrome
6. Henoch-Schonlein purpura
7. Paraproteinemias
8. Hereditary hemorrhagic telangiectasia (Osler-Rendu-Weber disease)
Disorders of Blood Coagulation
Congenital Disorders
1. Hemophilia A-incidence 1:5000, sex-linked recessive deficiency of factor VIII (low plasma factor VIII (low plasma factor VIII coagulant activity, but normal amount of factor VIII-related antigen-vWF). Laboratory features, elevated PTT, normal PT).
2. Hemophilia B (Christmas disease)-incidence 1:30.000, sex linked recessive, due to factor IX deficiency. Clinical and laboratory features similar to hemophilia A.
3. Von Willebrand disease-most common inherited coagulation disorder (1:800-1000), usually autosomal dominant, primary defect is reduced synthesis or chemically abnormal factor VIII-related antigen produced by platelets and endothelium, resulting in abnormal platelet function.
Acquired Disorders
1. Vitamin K deficiency-impairs production of factors II (prothrombin), VII, IX, and X, vitamin K is a cofactor in carboxylation of glutamate residues on prothrombin complex proteins, major source of vitamin K is dietary (esp. green vegetables), with minor production by gut bacteria. Laboratory features : elevated PT and PTT.
2. Liver disease – results in deficiencies of all clotting factor except VIII. Laboratory features : elevated PT, normal or elevated PTT.
3. Other disorders-DIC, fibrinogen deficiency (liver disease,L-asparaginase therapy, rattlesnake bites), other factor deficiencies, circulating anticoagulants (lymphoma, SLE, idiopathic), massive transfusion coagulopathy).
17th Edition Harrison’s Manual of Medicine, 2009 Chap. 68. Bleeding and Thrombotic Disorders p. 332
For more detailed, see
Konkle BA : Bleeding and Thrombosis, Chap 59, p.363
Konkle BA : Disorders of platelets and Vessel Wall, chap 109, p. 718
Arruda V, High KA : Coagulation Disorders, chap 110, p.725
Weititz JI : Antiplatelet, Anticoagulant, and Fibrionolytic Drugs, chap 112, p. 735, in HPIM-17
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