APPROACH TO THROMBOCYTOPENIA.pptx
- 1. MODERATOR:- DR. ALPIKA SHUKLA (ASSOCIATE PROFESSOR OF MEDICINE) GSVM MEDICAL COLLEGE PRESENTED BY:- SOUBHAGYA RANJAN DAS JR-1 MEDICINE APPROACH TO THROMBOCYTOPENIA
- 2. NORMAL PHYSIOLOGY OF PLATELETS Platelets are normally made in the bone marrow from progenitor cells known as megakaryocytes. Normal platelet lifespan is 10days & everyday 1/10th platelet pool is replenished. Normal platelet count is 150,000-450,000/ mm³ Contain intracellular granules (alpha and delta) that contain coagulation factors and ADP. Production stimulated by thrombopoietin from liver/kidney.
- 3. Reticulated platelets The youngest platelets in the circulation contain RNA and called as Reticulated platelets or the immature platelet fractions(IPF). Measurement of the percentage of reticulated platelets identifies platelets that have recently been released from the bone marrow . Normal subjects :- 1.3% There is an increased percentage of reticulated platelets in patients with thrombocytopenia caused by increased destruction . A normal to reduced percentage of reticulated platelets in patients with deficient production.
- 4. THROMBOCYTOPENIA Thrombocytopenia may be defined as a subnormal number of platelets in the circulating blood. Normal platelet count :- 150,000- 450,000/microlitre It is the most common cause of abnormal bleeding.
- 5. How low is too low? 150,000-50,000:- No symptoms 50,000-20,000:- first symptoms appear 20,000-10,000:- potentially life threatening. <10,000:- spontaneous intracranial hemorrhage.
- 6. Pathophysiologic classification of thrombocytopenia 1.Artifactual thrombocytopenia :- -Platelet clumping caused by anticoagulant-dependent immunoglobulin (pseudothrombocytopenia) -Platelet satellitism -Giant platelets
- 7. 2. Decreased platelet production :- a.Marrow Hypoplasia:- -After viral infections(Dengue,Rubella,Mumps,Varicella,Parvo,HCV,EBV,HIV) -Childhood bone marrow failure syndromes e.g- fanconi’s anemia -Idiopathic aplastic anemia - Drug induced( cytotoxics, antimetabolites)
- 8. b. Marrow infiltration:- -Leukemia, myeloma, carcinoma, myelofibrosis c.Haematinic deficiency:- -vit B12 and/or folate deficiency d.Familial (macro)thrombocytopathies:- -Myosin heavy chain abnormalities e.g- alport’s syndrome
- 9. 3. Increased platelet destruction:- a.Caused by immunologic processes:- -Autoimmune i.Primary (Immune Thrombocytopenia) ii.Secondary (Infections, pregnancy, collagen vascular disorders,lymphoproliferative disorders, drugs*) -Alloimmune i.Neonatal thrombocytopenia ii.Post-transfusion purpura
- 10. Drugs causing thrombocytopenia Abciximab Acetaminophen Amiodarone Amlodipine Ampicillin Carbamazepine Ceftriaxone Cephamandole Ciprofloxacin Diazepam Eptifibatide Furosemide Gold Haloperidol Heparin Ibuprofen Lorazepam Mirtazapine Naproxen Oxaliplatin Penicillin Phenytoin Piperacillin Quinine Quinidine Ranitidine Rosiglitazone Roxifiban Sulfisoxazole Suramin Tirofiban Tranilast Trimethoprim/sulfamethoxazole Vancomycin
- 11. b.Caused by Nonimmunologic processes:- -Thrombotic microangiopathies -Disseminated intravascular coagulation -Thrombotic thrombocytopenic purpura -Hemolytic-uremic syndrome -Platelet damage by abnormal vascular surfaces -Miscellaneous -Infection -Massive blood transfusions
- 12. 4. Abnormal platelet distribution or pooling:- - Disorders of the spleen (neoplastic, congestive, infiltrative, infectious, of unknown cause) -Hypothermia -Dilution of platelets with massive transfusions
- 13. Approach 1. History :- Onset(new/chronic/relapsing) Recent medication and vaccination Recent transfusion(hemodilution) Recent organ transplant Autoimmune disease/malignancy Pregnancy Travel history(malaria,rickettsia,dengue) Dietary habit(megaloblastic anemia) Ingeston of alcohol/quinine containing beverages
- 14. 2. Clinical Examination:- a. Look for petechiae,purpura or superficial bleeding. b. Joint or soft tissue bleeding-DIC c. Ischemic limb/skin necrosis-HIT d. Examine for hepatosplenomegaly and lymphadenopathies e. Presence of retinal hemorrhage on occular fundus examination is a predictor of CNS hemorrhage
- 15. Investigations
- 16. IMMUNE THROMBOCYTOPENIA The syndrome of ITP is caused by platelet-specific autoantibodies that bind to autologous platelets, which are then rapidly cleared from the circulation by the mononuclear phagocyte system via macrophage Fcγ receptors predominantly in the spleen and liver. 1. Primary:-It refers to thrombocytopenia in which apparent exogenous etiologic factors are lacking and in which diseases known to be associated with secondary thrombocytopenia have been excluded 2.Secondary:-If associated with other underlying causes.
- 17. features Acute ITP Chronic ITP Peak age of incidence Children, 2-6 y Adults, 20-40 y Sex predilection None 3:1 female to male Antecedent infection Common 1-3 wk before Unusual Onset of bleeding Abrupt Insidious Hemorrhagic bullae in mouth Present in severe cases Usually absent Platelet count <20,000/µl 30,000-80,000/µl Eosinophilia and lymphocytosis Common Rare Duration 2-6 wk; rarely longer Months or years Spontaneous remissions Occur in 80% of cases Uncommon
- 18. History Findings Disorder of platelets Disorder of coagulation Petechia Characteristic Rare Deep dissecting hematomas Rare Characteristics Superficial ecchymoses Characteristics Common Hemarthrosis Rare Characeristic Delayed bleeding Rare Common Bleeding from superficial cuts and scratches Persistent : often profuse Minimal Sex of patient Relately more common in females 80-90% in males Positive family history Rare(except vWD & hereditary hemorrhagic telengectesia) common
- 19. Clinical manisfestations Bleeding - Petechiae - Purpura: Dry(cutaneous) or wet(mucosal bleed) -Epistaxis -Severe hemorrhage: ICH, UGI bleed, Menorrhagia
- 20. Diagnosis The diagnosis of ITP is usually a diagnosis of exclusion based on a demonstration of peripheral thrombocytopenia, with a history, physical examination, and complete blood count that do not suggest another cause for the thrombocytopenia. Laboratory testing is performed to evaluate for secondary causes of ITP and should include testing for HIV infection and hepatitis C (and other infections if indicated). Serologic testing for SLE, serum protein electrophoresis, immunoglobulin levels to potentially detect hypogammaglobulinemia, selective testing for IgA deficiency or monoclonal gammopathies, and testing for H. pylori infection should be considered, depending on the clinical circumstance. If anemia is present, direct antiglobulin testing (Coombs’ test) should be performed to rule out combined autoimmune hemolytic anemia with ITP (Evans’ syndrome)
- 21. Treatment New diagnosis of ITP Platelet count> 20-30000/µL No treatment in the absence of special circumstances Inital treatment for plt count <20,000/µL Prednisone(1mg/kg/d) or dexa(40mg/day x 4days) ±IV anti-D(µg/kg) ±IVIG(1g/kg/day x 1-2days) Treatment for refractory thrombocytopenia <20,000/µL Splenectomy Thrombopoeitin mimetics -Eltrombopag(50mg/kg) -Romiplostim(1-10mcg/kg SC weekly) Rituximab (375mg/m² IV weekly x 4wk) Stable patient count >30-50,000/µL No therapy, observe
- 22. Emergency -IV methylpred(1g/day) x 3days + -IVIG(1g/kg/d) x 1-2days ±anti-D(50-75µg/kg) ±IV vincristine(1-2mg) ±platelet transfusion ±factor VIIa
- 23. SPLENECTOMY INDICATION:- Failed corticosteroid therapy. Single best option to convert a patient with ITP into “non-patient”. Approximately 85% patient attain a hemostatic response after splenectomy. Immunize with polyvalent pneumococcal, H. Infleunza type-B and meningococal polysachharide vaccine atleast 2wk prior to splenectomy if possible.
- 24. Inherited thrombocytopenia Causes:- 1.Small paltelets: -wiskott-aldrich syndrome 2. Normal sized platelets: -Throbocytopenia absent radii(TAR) syndrome -congenital amegakaryotic thrombocytopenia 3.Giant platelets: -MYH syndrome *May-Hegglin anomaly *Sebastian syndrome *Epstein’s syndrome *Fechtner syndromes - bernaurd soulier syndrome, gray platelet syndrome, montreal platelet syndrome
- 25. Thrombotic Thromocytopenic Purpura An inherited or acquired defciency(due to autoantibodies) of von Willebrandfactor-cleaving protease known as ADAMTS13. Leads to accumulation of large multimer of VWF which cause spontaneous platelet aggregation or thrombi. Can be induced by drugs. Increased incidence with pregnancy or HIV>
- 26. TTP- Diagnostic features *Microangiopathic Hemolytic Anemia(MAHA) -Elevated LDH, elevated bilirubin -schistocytes on peripheral smear(MUST BE PRESENT) *Low platelet(MUST BE PRESENT) *fever *Neurologic symptoms:- headache,sleepiness,confusion, stupor,stroke,coma,seizures. *Renal manifestations:- hematuria,protienuria elevated creatinine,BUN *CBC normal or slightly elevate WBC *Hb is moderately decreased 8-9 g/dL *Platelet ranges from 20,000- 50,000 *RBC are fragmented and appears as schistocytes *Decreased Haptoglobin *Increased Reticulocyte count *Negative direct anti globulin test
- 27. Treatment Therapeutic plasma exchange (TPE) remains the mainstay of treatment of TTP. TPE is continued until the platelet count is normal and signs of hemolysis are resolved for at least 2 days. Plasma infusion is used as an emergent substitute until plasma exchange is available. Addition of rituximab to initial therapy decreases duration of TPE and relapses.
- 28. Hemolytic Uremic Syndrome(HUS) HUS is a syndrome characterized by:- 1. Acute renal failure 2. Microangiopathic hemolytic anemia 3. Thrombocytopenia -Predominantly affects children. -TYPES:- a.Typical HUS b. Atypical HUS c.HUS due to complement abnormalities.
- 29. Typical/Diarrhea associated/Shiga toxin associated HUS:- Enterohaemorrhagic E.coli Shigella dysenteria type-I Common serotype of E.coli:o157:H7 Sources of infection are: - Milk & animal products - Human feco-oral transmission
- 30. Atypical/Non-Diarrhea related HUS Pnuemococcal HUS HUS due to complement abnormalities Miscellaneous causes of HUS/TTP -Abnormalities in intracllular vit.B12 metabolism -HIV -SLE -Malignancies -Radiation -Certain Drugs
- 31. Other infections associated with HUS:- -Influenza -CMV -Infectious mononucleosis -Salmonella -streptococcus
- 32. Diagnosis Clinically,HUS can be very difficult to distinguish from TTP. features TTP HUS Age Adult Children <5yr MAHA Present Present Thrombocytopenia Present Present Fever Present Absent Severe renal failure Uncommon Common Major neurological abnormalities Common Uncommon Prodrome bloody diarrhea Absent Present (typical HUS) Cause Severe deficiency of ADAMTS13 Infection by E.coli O157:H7 Coagulation test Normal Normal Treatment Plasma exchange Supportive
- 33. Treatment Treatment of HUS is primarily supportive. In patients with aHUS, eculizumab, a humanized monoclonal antibody against C5 that blocks terminal complement, has efficacy in resolution of aHUS and improving or preserving renal function.
- 34. Heparin Induced Thrombocytopenia HIT, also known as the white clot syndrome, is increasingly recognized as a potentially severe, albeit paradoxical, immune-mediated complication of heparin therapy. Drug-induced thrombocytopenia due to heparin differs from that seen with other drugs in two major ways:- 1. The thrombocytopenia is not usually severe, with nadir counts rarely <20,000/µL. 2. Heparin-induced thrombocytopenia (HIT) is not associated with bleeding and, in fact, markedly increases the risk of thrombosis. Mechanism of thrombocytopenia:-Antibody formation to a complex of the PF4 and Heparin.
- 35. Diagnosis 4 T’s in diagnosis of HIT:- a.Thrombocytopenia(rarely 20,000) b.Timing of platelet drop: witin 5-14 days of heparin exposure c.Thrombosis d.other causes of Thrombocytopenia ruled out
- 36. Treatment The initial treatment of HIT with or without thrombosis is to discontinue all exposure to heparin or LMWHs (including heparin-coated catheters) and immediately begin an alternative anticoagulant, usually a DTI, such as argatroban, lepirudin, or bivalirudin). Consider anticoagulation even in absence of thrombosis. If thrombosis present: warfarin for 3month, started only with overlap of DTI or Fondaparinux and after resolution of thrombocytopenia.