History

Fact Explanation
Introduction Immune thrombocytopenic purpura is a condition associated with autoantibody production(IgG) against one or more glycoproteins(eg; GPIIb, GPIIIa, Ib complex) in platelet membrane causing premature platelet destruction leading to thrombocytopenia. There is an autoantibody specificity against this glycoproteins[1]. This premature platelet destruction is done by monocyte- macrophage system. In children this condition usually occur following a viral infection as a sudden onset bruising or with spontaneous mucosal bleeding. In adults this has an insidious onset, common among females and will remain as a chronic relapsing and remitting disease.
History of suggestive of increased bleeding tendency Patient will present with multiple bruises, groups of pinpoint-sized dots on the skin and some times with bleeding from mucus membranes like gum bleeding, nasal bleeding[1].
Neurologic manifestations Neurologic manifestations such as alteration in mental status like confusion and drowsiness, seizures, muscle paralysis, paresthesias, blurred vision and headache will develop following intracranial haemorrhages. This is rare and only occur in severe cases with the platelet count less than 10 × 109/L[2] .
Easy fatigue, shortness of breath, tiredness Theae features suggestive of anaemia may be present in patients with bleeding. Bleeding causes iron deficiency anaemia[3].
History suggestive of a recent viral infection few weeks back Immune Thrombocytopenic Purpura can present following a viral infection like upper respiratory tract infection( cough, earache, throat ache, nasal congestion) and diarrhoeal illness. This is a common presentation in paediatric population[4]. Some viral infections like dengue, epstein-Barr virus, varicella virus, cytomegalo virus, rubella virus and hepatitis virus also can cause induce thrombocytopenia[6][7][8].
Past medical history If the patient is a diagnosed patient with Immune Thrombocytopenic Purpura full history about previous episodes need to be taken like exacerbating factors, severity of previous episodes and treatments given[4]. past medical history of some systemic illnessess like SLE, antiphospholipid syndrome, myelodysplastic syndrome, acute and chronic Leukemia(adults),Hodgkin’s disease, non-Hodgkin’s lymphomas and large granulocytic leukemia and Primary immunodeficiency conditions in children[13][14].
Immunization history Transient thrombocytopenia is some times associated with vaccination( eg; live attenuated vaccines like MMR, and influenza vaccine)[9][10][4].
Drug history Some drugs like chemotherapy causes generalzed myelosuppression causing platelet reduced platelet production and drugs like thiazide diuretics, ethanol and tolbutamide causes isolated thrombocytopenia by selective suppression of megakaryocyte production.some antineoplastic drus are leads to premature platelet dystruction ultimately causing thrombocytopenia[4][11][12].
References
  1. CINES DB, BUSSEL JB, LIEBMAN HA, LUNING PRAK ET. The ITP syndrome: pathogenic and clinical diversity Blood [online] 2009 Jun 25, 113(26):6511-6521 [viewed 25 September 2014] Available from: doi:10.1182/blood-2009-01-129155
  2. LILLEYMAN JS. Intracranial haemorrhage in idiopathic thrombocytopenic purpura. Paediatric Haematology Forum of the British Society for Haematology. Arch Dis Child [online] 1994 Sep, 71(3):251-253 [viewed 25 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1029982
  3. NOONAVATH RN, LAKSHMI CP, DUTTA TK, KATE V. Helicobacter pylori eradication in patients with chronic immune thrombocytopenic purpura World J Gastroenterol [online] 2014 Jun 14, 20(22):6918-6923 [viewed 25 September 2014] Available from: doi:10.3748/wjg.v20.i22.6918
  4. CINES DB, LIEBMAN H, STASI R. Pathobiology of secondary immune thrombocytopenia Semin Hematol [online] 2009 Jan, 46(1 Suppl 2):S2-14 [viewed 25 September 2014] Available from: doi:10.1053/j.seminhematol.2008.12.005
  5. STASI R. Pathophysiology and therapeutic options in primary immune thrombocytopenia Blood Transfus [online] 2011 Jul, 9(3):262-273 [viewed 27 September 2014] Available from: doi:10.2450/2010.0080-10
  6. KHAN ASSIR MZ, KAMRAN U, AHMAD HI, BASHIR S, MANSOOR H, ANEES SB, AKRAM J. Effectiveness of Platelet Transfusion in Dengue Fever: A Randomized Controlled Trial Transfus Med Hemother [online] 2013 Oct, 40(5):362-368 [viewed 27 September 2014] Available from: doi:10.1159/000354837
  7. DANISH FA, KOUL SS, SUBHANI FR, RABBANI AE, YASMIN S. Considerations in the Management of Hepatitis C Virus-related Thrombocytopenia with Eltrombopag Saudi J Gastroenterol [online] 2010, 16(1):51-56 [viewed 27 September 2014] Available from: doi:10.4103/1319-3767.58772
  8. STEEPER TA, HORWITZ CA, MOORE SB, HENLE W, HENLE G, ELLIS R, FLYNN PJ. Severe thrombocytopenia in Epstein-Barr virus-induced mononucleosis. West J Med [online] 1989 Feb, 150(2):170-173 [viewed 27 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1026329
  9. CECINATI V, PRINCIPI N, BRESCIA L, GIORDANO P, ESPOSITO S. Vaccine administration and the development of immune thrombocytopenic purpura in children Hum Vaccin Immunother [online] 2013 May 1, 9(5):1158-1162 [viewed 27 September 2014] Available from: doi:10.4161/hv.23601
  10. BLACK C, KAYE JA, JICK H. MMR vaccine and idiopathic thrombocytopaenic purpura Br J Clin Pharmacol [online] 2003 Jan, 55(1):107-111 [viewed 27 September 2014] Available from: doi:10.1046/j.1365-2125.2003.01790.x
  11. TRINKAUS M, TRUDEAU M, CALLUM J. Drug-induced immune thrombocytopenic purpura secondary to sunitinib Curr Oncol [online] 2008 Jun, 15(3):152-154 [viewed 28 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2442762
  12. VISENTIN GP, LIU CY. 9. Drug Induced Thrombocytopenia Hematol Oncol Clin North Am [online] 2007 Aug, 21(4):685-vi [viewed 28 September 2014] Available from: doi:10.1016/j.hoc.2007.06.005
  13. IZAK M, BUSSEL JB. Management of thrombocytopenia F1000Prime Rep [online] :45 [viewed 28 September 2014] Available from: doi:10.12703/P6-45
  14. KISTANGURI G, MCCRAE KR. Immune Thrombocytopenia Hematol Oncol Clin North Am [online] 2013 Jun, 27(3):495-520 [viewed 28 September 2014] Available from: doi:10.1016/j.hoc.2013.03.001

Examination

Fact Explanation
Signs of increase bleeding tendency There will be multiple purpura/ ecchymotic patches and groups of petechiae and evidence of gum/ nasal bleeding or bleeding from other mucus membranes( gastrointestinal bleeding will present as either malena/ haematochaezia or haemoptysis, genitourinary bleeding will give haematuria). If patient develop retroperitoneal/ intraperitoneal bleeding there will be signs of acute abdomen (tender abdomen, garding, rigidity and psoas sign). If there is muscle bleeding muscle tenderness will be present. Usually bleeding manifestations are rare with this condition other than skin manifestations and patient will be other wise healthy in physical examination if there are no associated complications[1]. Rare but serious intracranial haemorrhages can also be a presentation and will discuss separately[3].
Pallor This is rare and can associated secondary to excessive bleeding following thrombocytopenia[2]. Also useful in ruling out other primary causes like chronic systemic illnessess (SLE, antiphospholipid syndrome, myelodyasplastic syndrome) leading to thrombocytopenia[5][6].
Neurologic examination Neurologic examination reveals alteration in mental status( confusion/ drowsiness), development of seizures, hemiplegia, paresthesias, visual disturbance following an intracranial haemorrhage[3]. Recent asymmetrical findings in neurological examination will suggest intra creanial haemorrhages in patients with ITP.
Fundoscopic examination This will reveals the presence of any retinal haemorrhages and vitreous haemorrhages. If the patient is having increased intracranial pressure following intra cranial haemorrhages there will be papilloedema [4][7].
Splenomegaly Splenomegaly is not a typical presentation in this condition but can occur following increased platelet destruction. But if splenomegaly is present, need to exclude other causes which are associated with splenomegaly like thrombotic thrombocytopenia purpura[8].
Fever, ill health, cough, skin rash, lympadenopathy suggestive of recent viral infection Some viral infections like dengue, epstein-Barr virus, varicella virus, cytomegalo virus, rubella virus and hepatitis virus also can cause induce thrombocytopenia[9][10][11].
Skin rashes, oral ulcers, lymphadenopathy, joint inflammation, low grade fever, oral trush, hepatospenomegaly and anaemia like features suggestive of sysrtemic illnessess. As systemic illnessess like SLE, antiphospholipid syndrome, myelodysplastic syndrome, acute and chronic Leukemia(adults),Hodgkin’s disease, non-Hodgkin’s lymphomas and large granulocytic leukemia and Primary immunodeficiency conditions in children can induce thrombocytopenia these conditions need to be excluded[12][13]. 7) Immunization history Transient thrombocytopenia is some times associated with vaccination( eg; live attenuated vaccines like MMR, and influenza vaccine)[9][10][4]. 8) Drug history Some drugs like chemotherapy causes generalzed myelosuppression causing platelet reduced platelet production and drugs like thiazide diuretics, ethanol and tolbutamide causes isolated thrombocytopenia by selective suppression of megakaryocyte production.some antineoplastic drus are leads to premature platelet dystructio
Hypertension and bradycardia. This combination will suggest the increased intracranial pressure. In here Increased intracranial pressure exceeds the mean arterial pressure and cerebral perfusion get diminished, which leads activation of sympathetic system which causes hypertension and tachycardia initially via alpha 1 receptors. Mean while the baroreceptors get stimulated and causes bradycardia via vagal stimulation[14].
References
  1. CINES DB, BUSSEL JB, LIEBMAN HA, LUNING PRAK ET. The ITP syndrome: pathogenic and clinical diversity Blood [online] 2009 Jun 25, 113(26):6511-6521 [viewed 25 September 2014] Available from: doi:10.1182/blood-2009-01-129155
  2. NOONAVATH RN, LAKSHMI CP, DUTTA TK, KATE V. Helicobacter pylori eradication in patients with chronic immune thrombocytopenic purpura World J Gastroenterol [online] 2014 Jun 14, 20(22):6918-6923 [viewed 25 September 2014] Available from: doi:10.3748/wjg.v20.i22.6918
  3. LILLEYMAN JS. Intracranial haemorrhage in idiopathic thrombocytopenic purpura. Paediatric Haematology Forum of the British Society for Haematology. Arch Dis Child [online] 1994 Sep, 71(3):251-253 [viewed 25 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1029982
  4. MAJJI AB, BHATIA K, MATHAI A. Spontaneous bilateral peripapillary, subhyaloid and vitreous hemorrhage with severe anemia secondary to idiopathic thrombocytopenic purpura Indian J Ophthalmol [online] 2010, 58(3):234-236 [viewed 25 September 2014] Available from: doi:10.4103/0301-4738.62651
  5. IZAK M, BUSSEL JB. Management of thrombocytopenia F1000Prime Rep [online] :45 [viewed 28 September 2014] Available from: doi:10.12703/P6-45
  6. KISTANGURI G, MCCRAE KR. Immune Thrombocytopenia Hematol Oncol Clin North Am [online] 2013 Jun, 27(3):495-520 [viewed 28 September 2014] Available from: doi:10.1016/j.hoc.2013.03.001
  7. RANGEL-CASTILLO L, GOPINATH S, ROBERTSON CS. Management of Intracranial Hypertension Neurol Clin [online] 2008 May, 26(2):521-541 [viewed 28 September 2014] Available from: doi:10.1016/j.ncl.2008.02.003
  8. KüHNE T, BERCHTOLD W, MICHAELS LA, WU R, DONATO H, ESPINA B, TAMARY H, RODEGHIERO F, CHITLUR M, RISCHEWSKI J, IMBACH P. Newly diagnosed immune thrombocytopenia in children and adults: a comparative prospective observational registry of the Intercontinental Cooperative Immune Thrombocytopenia Study Group Haematologica [online] 2011 Dec, 96(12):1831-1837 [viewed 28 September 2014] Available from: doi:10.3324/haematol.2011.050799
  9. KHAN ASSIR MZ, KAMRAN U, AHMAD HI, BASHIR S, MANSOOR H, ANEES SB, AKRAM J. Effectiveness of Platelet Transfusion in Dengue Fever: A Randomized Controlled Trial Transfus Med Hemother [online] 2013 Oct, 40(5):362-368 [viewed 27 September 2014] Available from: doi:10.1159/000354837
  10. DANISH FA, KOUL SS, SUBHANI FR, RABBANI AE, YASMIN S. Considerations in the Management of Hepatitis C Virus-related Thrombocytopenia with Eltrombopag Saudi J Gastroenterol [online] 2010, 16(1):51-56 [viewed 27 September 2014] Available from: doi:10.4103/1319-3767.58772
  11. STEEPER TA, HORWITZ CA, MOORE SB, HENLE W, HENLE G, ELLIS R, FLYNN PJ. Severe thrombocytopenia in Epstein-Barr virus-induced mononucleosis. West J Med [online] 1989 Feb, 150(2):170-173 [viewed 27 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1026329
  12. IZAK M, BUSSEL JB. Management of thrombocytopenia F1000Prime Rep [online] :45 [viewed 28 September 2014] Available from: doi:10.12703/P6-45
  13. KISTANGURI G, MCCRAE KR. Immune Thrombocytopenia Hematol Oncol Clin North Am [online] 2013 Jun, 27(3):495-520 [viewed 28 September 2014] Available from: doi:10.1016/j.hoc.2013.03.001
  14. BRAGIN DE, BUSH RC, MüLLER WS, NEMOTO EM. High Intracranial Pressure Effects on Cerebral Cortical Microvascular Flow in Rats J Neurotrauma [online] 2011 May, 28(5):775-785 [viewed 28 September 2014] Available from: doi:10.1089/neu.2010.1692

Differential Diagnoses

Fact Explanation
Thrombotic Thrombocytopenic Purpura Thrombotic Thrombocytopenic Purpura is a haematological disorder. It is characterized by thrombus formation in small blood vessels of the body. As thrombus consume platelets in the blood it causes reduction in platelet count (thrombocytopenia). So there ia a bleeding tendency associated with this disease[1]. But in Immune Thrombocytopenic Purpura there will be only bleeding manifestations and there won't be any thrombotic complications[6].
Disseminated Intravascular Coagulation In Disseminated intravascular coagulation there is generalized activation of blood clotting leading to systemic thrombus formation. These microvascular thrombi in all over the body will leads to multiple organ failure. Following this excessive consumption of coagulation factors and platelets there will be lack of clotting ability in circulation causing severe bleeding[2].Immune Thrombocytopenic Purpura will not have thrombotic complications[6].
Haemolytic uremic syndrome Hemolytic uremic syndrome is a common cause of acute renal failure and this condition characterized by progressive renal failure( due to microangiopathic hemolytic anemia) and thrombocytopenia[3]. Immune Thrombocytopenic Purpura will only have thrombocytopenia[6].
Myelodysplastic Syndrome There is a disorder in multipotent haemopoietic stem cells causing bone marrow failure. This leads to abnormalities in all cell lines causing anaemia, thrombocytopenia and leucopenia[4]. Immune Thrombocytopenic Purpura only associate with thrombocytopenia[6].
Hypersplenism With splenomegaly there will be pooling of blood inside the spleen causing thrombocytopenia[5]. Usually this will not associated with bleeding manifestations like in Immune Thrombocytopenic Purpura[6].
References
  1. TSAI HM. Pathophysiology of thrombotic thrombocytopenic purpura Int J Hematol [online] 2010 Jan, 91(1):1-19 [viewed 25 September 2014] Available from: doi:10.1007/s12185-009-0476-1
  2. FRANCHINI M, LIPPI G, MANZATO F. Recent acquisitions in the pathophysiology, diagnosis and treatment of disseminated intravascular coagulation Thromb J [online] :4 [viewed 25 September 2014] Available from: doi:10.1186/1477-9560-4-4
  3. MAYER CL, LEIBOWITZ CS, KUROSAWA S, STEARNS-KUROSAWA DJ. Shiga Toxins and the Pathophysiology of Hemolytic Uremic Syndrome in Humans and Animals Toxins (Basel) [online] , 4(11):1261-1287 [viewed 25 September 2014] Available from: doi:10.3390/toxins4111261
  4. JäDERSTEN M. Pathophysiology and treatment of the myelodysplastic syndrome with isolated 5q deletion Haematologica [online] 2010 Mar, 95(3):348-351 [viewed 25 September 2014] Available from: doi:10.3324/haematol.2009.019141
  5. JANDL JH, ASTER RH, FORKNER CE, FISHER AM, VILTER RW. Splenic pooling and the pathophysiology of hypersplenism. Trans Am Clin Climatol Assoc [online] 1967:9-27 [viewed 25 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2441156
  6. CINES DB, BUSSEL JB, LIEBMAN HA, LUNING PRAK ET. The ITP syndrome: pathogenic and clinical diversity Blood [online] 2009 Jun 25, 113(26):6511-6521 [viewed 25 September 2014] Available from: doi:10.1182/blood-2009-01-129155

Investigations - for Diagnosis

Fact Explanation
Full blood count Platelet count is normally in between 10-50x 109/L. Usually other cell counts are normal. But if there is any ongoing infection there will be increase in WBC count and if the excessive bleeding is present there will be low haemoglobin levels due to iron deficiency anaemia[1].
Peripheral blood film examination Reduced number of platelet count will be present. Morphology of red blood cells and WBC will be normal in the absent of other complications[2].
Bone marrow biopsy This will show normal or increased levels of megakaryocytes. This bone marrow biopsy should be done before starting steroid treatment as it can interfere with the morphology of platelets. This is useful in excluding other differential diagnosis like myelodysplastic syndrome as well[3].
Tests for platelet antigen–specific antibodies, platelet-associated immunoglobulin and antiplatelet antibodies These tests are useful in assesing the presence of auto antibody levels in the body.Eg; antiglycoprotein GPIIb, IIIa or GPIb antibodies on platelet surface[4][5][6].
Antinuclear antibodies In a symptomatic chronic disease state, negativity of this will be useful in excluding other conditions and come to the diagnosis of chronic Immune Thrombocytopenic Purpura[7].
PT/INR, APTT As there is no clotting factor defect these tests are normal and helps in differentiating this bleeding tendency with other clotting disorders[9].
Computed tomography (CT) scanning and magnetic resonance imaging (MRI) CT scanning or MRI useful in the medical history or physical findings suggest serious internal bleeding[8].
References
  1. CINES DB, BUSSEL JB, LIEBMAN HA, LUNING PRAK ET. The ITP syndrome: pathogenic and clinical diversity Blood [online] 2009 Jun 25, 113(26):6511-6521 [viewed 25 September 2014] Available from: doi:10.1182/blood-2009-01-129155
  2. STAVROU E, MCCRAE KR. Immune Thrombocytopenia in Pregnancy Hematol Oncol Clin North Am [online] 2009 Dec, 23(6):1299-1316 [viewed 25 September 2014] Available from: doi:10.1016/j.hoc.2009.08.005
  3. BHASIN TS, SHARMA S, MANJARI M, MANNAN R, KANSAL V, CHANDEY M, PIPLANI S. Changes in Megakaryocytes in Cases of Thrombocytopenia: Bone Marrow Aspiration and Biopsy Analysis J Clin Diagn Res [online] 2013 Mar, 7(3):473-479 [viewed 25 September 2014] Available from: doi:10.7860/JCDR/2013/5085.2801
  4. KAHANE S, DVILANSKY A, ESTOK L, NATHAN I, ZOLOTOV Z, SAROV I. Detection of anti-platelet antibodies in patients with idiopathic thrombocytopenic purpura (ITP) and in patients with rubella and herpes group viral infections. Clin Exp Immunol [online] 1981 Apr, 44(1):49-56 [viewed 25 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1537229
  5. WINIARSKI J, EKELUND E. Antibody binding to platelet antigens in acute and chronic idiopathic thrombocytopenic purpura: a platelet membrane ELISA for the detection of antiplatelet antibodies in serum. Clin Exp Immunol [online] 1986 Feb, 63(2):459-465 [viewed 25 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1577386
  6. WINIARSKI J, HOLM G. Platelet associated immunoglobulins and complement in idiopathic thrombocytopenic purpura. Clin Exp Immunol [online] 1983 Jul, 53(1):201-207 [viewed 25 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1535552
  7. LEBANO R, ROSATO V, MASARONE M, ROMANO M, PERSICO M. The effect of antiviral therapy on hepatitis C virus-related thrombocytopenia: a case report BMC Res Notes [online] :59 [viewed 25 September 2014] Available from: doi:10.1186/1756-0500-7-59
  8. CHALELA JA, KIDWELL CS, NENTWICH LM, LUBY M, BUTMAN JA, DEMCHUK AM, HILL MD, PATRONAS N, LATOUR L, WARACH S. Magnetic resonance imaging and computed tomography in emergency assessment of patients with suspected acute stroke: a prospective comparison Lancet [online] 2007 Jan 27, 369(9558):293-298 [viewed 25 September 2014] Available from: doi:10.1016/S0140-6736(07)60151-2
  9. DASGUPTA A, RAI S, DAS GUPTA A. Persistently Elevated Laboratory Markers of Thrombosis and Fibrinolysis After Clinical Recovery in Malaria Points to Residual and Smouldering Cellular Damage Indian J Hematol Blood Transfus [online] 2012 Mar, 28(1):29-36 [viewed 25 September 2014] Available from: doi:10.1007/s12288-011-0106-y

Investigations - Fitness for Management

Fact Explanation
Full Blood Count Assess the degree of thrombocytopenia will helpful in deciding the patients present condition and also helpful as a test of assessing the fitness of patients awaiting for splenectomy[1].
Fasting blood sugar This is being done as a test of assessing the fitness of patients awaiting for splenectomy, to see the blood sugar control[3].
Renal function test including serum electrolytes, blood urea and serum creatinine These are tests used to assess the basic fitness of patients awaiting for splenectomy, to see the renal function of the patient[4].
Clotting profile including PT/INR, APTT This use to assess the clotting status of the patient and usually done as a test of assessing the fitness of patients awaiting for splenectomy[5].
ECG This is useful in assessing cardiovascular fitness and also helpful in diagnosis as the ECG leads(which induced a suction over the skin) can induce petechiae following bleeding from capillaries[4][6].
Computed tomography (CT) scanning and magnetic resonance imaging (MRI) CT scanning or MRI useful in the medical history or physical findings suggest serious internal bleeding[2].
References
  1. CINES DB, BUSSEL JB, LIEBMAN HA, LUNING PRAK ET. The ITP syndrome: pathogenic and clinical diversity Blood [online] 2009 Jun 25, 113(26):6511-6521 [viewed 25 September 2014] Available from: doi:10.1182/blood-2009-01-129155
  2. CHALELA JA, KIDWELL CS, NENTWICH LM, LUBY M, BUTMAN JA, DEMCHUK AM, HILL MD, PATRONAS N, LATOUR L, WARACH S. Magnetic resonance imaging and computed tomography in emergency assessment of patients with suspected acute stroke: a prospective comparison Lancet [online] 2007 Jan 27, 369(9558):293-298 [viewed 25 September 2014] Available from: doi:10.1016/S0140-6736(07)60151-2
  3. DESAKI R, MIZUNO S, TANEMURA A, KISHIWADA M, MURATA Y, AZUMI Y, KURIYAMA N, USUI M, SAKURAI H, TABATA M, ISAJI S. A New Surgical Technique of Pancreaticoduodenectomy with Splenic Artery Resection for Ductal Adenocarcinoma of the Pancreatic Head and/or Body Invading Splenic Artery: Impact of the Balance between Surgical Radicality and QOL to Avoid Total Pancreatectomy Biomed Res Int [online] 2014:219038 [viewed 27 September 2014] Available from: doi:10.1155/2014/219038
  4. BENARROCH-GAMPEL J, SHEFFIELD KM, DUNCAN CB, BROWN KM, HAN Y, TOWNSEND CM JR, RIALL TS. Preoperative Laboratory Testing in Patients Undergoing Elective, Low-Risk Ambulatory Surgery Ann Surg [online] 2012 Sep, 256(3):518-528 [viewed 27 September 2014] Available from: doi:10.1097/SLA.0b013e318265bcdb
  5. LIUMBRUNO GM, BENNARDELLO F, LATTANZIO A, PICCOLI P, ROSSETTI G, ITALIAN SOCIETY OF TRANSFUSION MEDICINE AND IMMUNOHAEMATOLOGY (SIMTI) WORKING PARTY. Recommendations for the transfusion management of patients in the peri-operative period. I. The pre-operative period Blood Transfus [online] 2011 Jan, 9(1):19-40 [viewed 27 September 2014] Available from: doi:10.2450/2010.0074-10
  6. BLOMBERY P, SCULLY M. Management of thrombotic thrombocytopenic purpura: current perspectives J Blood Med [online] :15-23 [viewed 27 September 2014] Available from: doi:10.2147/JBM.S46458

Investigations - Followup

Fact Explanation
Full Blood Count This is useful in follow up to see the level of thrombocytopenia[1].
Clotting profile with prothrombin time and activated partial thromboplastin time This is useful in excluding any associated clotting factor deficiency[3].
CT scanning /MRI CT scanning or MRI will useful in follow up in the medical history or physical findings suggest serious internal bleeding[2].
References
  1. CINES DB, BUSSEL JB, LIEBMAN HA, LUNING PRAK ET. The ITP syndrome: pathogenic and clinical diversity Blood [online] 2009 Jun 25, 113(26):6511-6521 [viewed 25 September 2014] Available from: doi:10.1182/blood-2009-01-129155
  2. CHALELA JA, KIDWELL CS, NENTWICH LM, LUBY M, BUTMAN JA, DEMCHUK AM, HILL MD, PATRONAS N, LATOUR L, WARACH S. Magnetic resonance imaging and computed tomography in emergency assessment of patients with suspected acute stroke: a prospective comparison Lancet [online] 2007 Jan 27, 369(9558):293-298 [viewed 25 September 2014] Available from: doi:10.1016/S0140-6736(07)60151-2
  3. DASGUPTA A, RAI S, DAS GUPTA A. Persistently Elevated Laboratory Markers of Thrombosis and Fibrinolysis After Clinical Recovery in Malaria Points to Residual and Smouldering Cellular Damage Indian J Hematol Blood Transfus [online] 2012 Mar, 28(1):29-36 [viewed 25 September 2014] Available from: doi:10.1007/s12288-011-0106-y

Investigations - Screening/Staging

Fact Explanation
ESR, CRP and disease specific serological antigens No specific test for screening the disease but as these patients are at risk of getting infections screening for infections can be done with ESR, CRP and disease specific serological antigens[1].
Enzyme immunoassay for HIV There is a relationship in between thrombocytopenia and HIv infection. The exact mechanism is not identified but there are suggestions about the pathophysiology. One is the direct HIV infection of the megakaryotypes leading to dystruction of cells. Another theory is HIV infection leads to production of abnormal megakaryocytes causing abnormal platelets. Also other theory says cross reaction of HIV antibodies with platelets leads to premature platelet destruction causing thrombocytopenia.In a blood picture of a HIV patient there are apoptic megakaryocytes and clustered megakaryocytes.
References
  1. CINES DB, LIEBMAN H, STASI R. Pathobiology of secondary immune thrombocytopenia Semin Hematol [online] 2009 Jan, 46(1 Suppl 2):S2-14 [viewed 25 September 2014] Available from: doi:10.1053/j.seminhematol.2008.12.005
  2. CINES DB, LIEBMAN H, STASI R. Pathobiology of secondary immune thrombocytopenia Semin Hematol [online] 2009 Jan, 46(1 Suppl 2):S2-14 [viewed 27 September 2014] Available from: doi:10.1053/j.seminhematol.2008.12.005
  3. DOMíNGUEZ A, GAMALLO G, GARCIA R, LOPEZ-PASTOR A, PEñA JM, VAZQUEZ JJ. Pathophysiology of HIV related thrombocytopenia: an analysis of 41 patients. J Clin Pathol [online] 1994 Nov, 47(11):999-1003 [viewed 27 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC503060

Management - General Measures

Fact Explanation
Health education Patient/ care givers should be aware about the condition, symptoms, treatment options complications and prognosis[1].
Post splenectomy care Patients are at risk of getting infections from encapsulated organisms. Vaccination should be done( against Haemophilus influenzae type b vaccine, polyvalent Streptococcus pneumoniae vaccine and meningococcal polysaccharide vaccine and annual influenza vaccine). Prevention, early diagnosis and early tratment for infections is also very important[2].
Antibiotic therapy As these patients are at risk of getting infections, if a patient present with fever they should be treated with IV antibiotics until excluding a bacterial infection excluded[3].
References
  1. CINES DB, BUSSEL JB, LIEBMAN HA, LUNING PRAK ET. The ITP syndrome: pathogenic and clinical diversity Blood [online] 2009 Jun 25, 113(26):6511-6521 [viewed 25 September 2014] Available from: doi:10.1182/blood-2009-01-129155
  2. KISTANGURI G, MCCRAE KR. Immune Thrombocytopenia Hematol Oncol Clin North Am [online] 2013 Jun, 27(3):495-520 [viewed 25 September 2014] Available from: doi:10.1016/j.hoc.2013.03.001
  3. CINES DB, LIEBMAN H, STASI R. Pathobiology of secondary immune thrombocytopenia Semin Hematol [online] 2009 Jan, 46(1 Suppl 2):S2-14 [viewed 25 September 2014] Available from: doi:10.1053/j.seminhematol.2008.12.005

Management - Specific Treatments

Fact Explanation
Observation If the patient is asymptomatic or present with mild bleeding observation alone is enough regardless of the platelet count of the patient[2].
corticosteroids like oral prednisone, intravenous [IV] methylprednisolone or high-dose dexamethasone This is the first line treatment in acute Immune Thrombocytopenic Purpura. Corticosteroids are useful in reducing the platelet destruction by auto antibodies by inducing immunosuppressive state. Also it is useful in repairing the endothelial damage and by that it maintain haemostasis and minimize bleeding[3].
IV immunoglobulin (IVIG) This is the second line medication following corticosteroid therapy. High dose of IV immunoglobulin helps in increasing platelet count rapidly by blocking receptors on macrophages or modifying autoantibody production. This is useful in life threatening haemorrhages, steroid refractory disease, pregnancy and before surgical procedures[1].
Immunosuppressive therapy( eg; cyclophosphamide, azothioprine) Theses drugs are use either individually or as combinations in patients who are not respond to other treatments[4].
Monoclonal antibody therapy Rituximab is also used in Immune Thrombocytopenic Purpura patients. This is also proven to be benefited in treatment[5].
Androgens( eg; Danazol) Androgens are known to increase platelet count by reducing the destruction of immunoglobulin-coated platelets and also by decreasing the auto antibody production. In here often necessary to combine with an immunosuppressive medication[6].
Thrombopoietin-Receptor Agonists This is a newer treatment option which is more important as it directly stimulate the platelet production via stimulating bone marrows[7].
Platelet transfusion This is useful in acute life threatening conditions but the benefit will last only for few hours[8].
Splenectomy This is recommended in symptomatic patients with platelet count less than 30x 109/L, after 3 months of steroid therapy. This is more effective in acute conditions but less effective in chronic status[9].
Stem cell transplantation This is identified as a curable treatment option in severe cases[10].
ITP management in pregnancy by monitoring and medical treatments. FBC should be done every 2-4 weekly to assess the level of thrombocytopenia. If patient is asymptomatic and platelet count is more than 50x 109/L , no treatment will be needed other than close monitoring. If the patient is having bleeding or platelet count is less than 50x 109/L oral steroid treatment will be useful. If patients condition is not improving with the steroids IV immunoglobuline need to be considered. Splenectomy is rarely indicated in pregnancy. Platelet transfusion will be useful where rapid correction is needed. close monitoring should be done as patient is at risk of antenatal and intrapartum bleeding During labour foetal scalp electrodes, foetal blood sampling, ventous delivery and rotational forceps delivery need to be avoided. Cord blood should be tested for platelet count( as IgG antiplatlet antibodies can cross the placenta and leads to foetal thrombocytopenia [11][12][13].
References
  1. CINES DB, BUSSEL JB, LIEBMAN HA, LUNING PRAK ET. The ITP syndrome: pathogenic and clinical diversity Blood [online] 2009 Jun 25, 113(26):6511-6521 [viewed 25 September 2014] Available from: doi:10.1182/blood-2009-01-129155
  2. KüHNE T, BERCHTOLD W, MICHAELS LA, WU R, DONATO H, ESPINA B, TAMARY H, RODEGHIERO F, CHITLUR M, RISCHEWSKI J, IMBACH P. Newly diagnosed immune thrombocytopenia in children and adults: a comparative prospective observational registry of the Intercontinental Cooperative Immune Thrombocytopenia Study Group Haematologica [online] 2011 Dec, 96(12):1831-1837 [viewed 25 September 2014] Available from: doi:10.3324/haematol.2011.050799
  3. EDEN OB, LILLEYMAN JS. Guidelines for management of idiopathic thrombocytopenic purpura. The British Paediatric Haematology Group. Arch Dis Child [online] 1992 Aug, 67(8):1056-1058 [viewed 25 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1793581
  4. PALAU J, JARQUE I, SANZ MA. Long-term management of chronic immune thrombocytopenic purpura in adults Int J Gen Med [online] :305-311 [viewed 25 September 2014] Available from: doi:10.2147/IJGM.S4722
  5. EL‐SHANAWANY TM, WILLIAMS PE, JOLLES S. Response of refractory immune thrombocytopenic purpura in a patient with common variable immunodeficiency to treatment with rituximab J Clin Pathol [online] 2007 Jun, 60(6):715-716 [viewed 25 September 2014] Available from: doi:10.1136/jcp.2006.041426
  6. EDELMANN DZ, KNOBEL B, VIRAG I, MEYTES D. Danazol in non-splenectomized patients with refractory idiopathic thrombocytopenic purpura. Postgrad Med J [online] 1990 Oct, 66(780):827-830 [viewed 25 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2429727
  7. SIEGAL D, CROWTHER M, CUKER A. Thrombopoietin Receptor Agonists in Primary ITP Semin Hematol [online] 2013 Jan, 50(0 1):S18-S21 [viewed 25 September 2014] Available from: doi:10.1053/j.seminhematol.2013.03.005
  8. KUTER DJ, GERNSHEIMER TB. Thrombopoietin and Platelet Production in Chronic Immune Thrombocytopenia Hematol Oncol Clin North Am [online] 2009 Dec, 23(6):1193-1211 [viewed 25 September 2014] Available from: doi:10.1016/j.hoc.2009.09.001
  9. AKWARI OE, ITANI KM, COLEMAN RE, ROSSE WF. Splenectomy for primary and recurrent immune thrombocytopenic purpura (ITP). Current criteria for patient selection and results. Ann Surg [online] 1987 Oct, 206(4):529-541 [viewed 25 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1493222
  10. POON LM, STASI AD, POPAT U, CHAMPLIN RE, CIUREA SO. Romiplostim for delayed platelet recovery and secondary thrombocytopenia following allogeneic stem cell transplantation Am J Blood Res [online] , 3(3):260-264 [viewed 25 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3755526
  11. STAVROU E, MCCRAE KR. Immune Thrombocytopenia in Pregnancy Hematol Oncol Clin North Am [online] 2009 Dec, 23(6):1299-1316 [viewed 27 September 2014] Available from: doi:10.1016/j.hoc.2009.08.005
  12. ANGLIN BV, RUTHERFORD C, RAMUS R, LIESER M, JONES DB. Immune Thrombocytopenic Purpura During Pregnancy: Laparoscopic Treatment JSLS [online] 2001, 5(1):63-67 [viewed 27 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3015411
  13. NICOLESCU A, VLADAREANU AM, VOICAN I, ONISAI M, VLADAREANU R. Therapeutic Options for Immune Thrombocytopenia (ITP) During Pregnancy Maedica (Buchar) [online] 2013 Jun, 8(2):182-188 [viewed 27 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3865128