History

Fact Explanation
Introduction 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)[5]. So there ia a bleeding tendency associated with this disease.
History of suggestive of increased bleeding tendency Patient will present with multiple bruises on the skin/mucous membranes, groups of pinpoint-sized dots on the skin and bleeding from mucus membranes like gum bleeding, nasal bleeding, per rectal bleeding, menorrhagia and haematuria[1]. Bleeding under the skin/ mucous membranes will leads to these purpura and petechiae[1].
Easy fatigue, shortness of breath, tiredness This condition is associated with microangiopathic hemolytic anemia which is a caused by red blood cell destruction with mechanical injury while passing throught thrombus formed blood vessls . This causes fragmentation of red blood cells and hemolysis[3] giving features of anaemia[1].
Yellowish discoloration of eyes This is due to the excessive destruction of red blood cells causing jaundice[2].
dark red urine from hemoglobinuria With microangiopathic hemolytic anemia, red blood cells are become fragments and destroyed[1],. Whith this excessive haemolysis free plasma haemoglobin level is increased and they filtere via kidneys causing hemoglobinuria[4].
low/ none urine out put, red colored urine and/ or frothy urine Oliguria/anuria , haematuria and protein urea are presentations in renal involvement. Focal/segmental microthrombi formation is the common reason in here for renal failure[3].
Neurologic manifestations Neurologic manifestations such as alteration in mental statuslike confusion and drowsiness, seizures, muscle paralysis, paresthesias, visual problems and headache. With extensive microthrombil formation in various parts of the brain will leads to these neurological manifestations. Brain ischemia causing transient ischemic attacks and strokes are common in this patients[3].
History of episodic exacerbations Fever, infections, diarrheal conditions, trauma, surgery or pregnancy like stressful situations are common precipitating factors[3][5].According to available data In this condition fever occurs in approximately half of the patients. Some drugs[7] like cyclosporin A, cisplatin and quinine are identified to be associated with Thrombotic Thrombocytopenic Purpura.
sudden onset abdominal pain, nausea and vomiting[3] As this is a mutisystem disease this can affect bowel causing bowel ischemia with thrombi formation leading to these symptoms[8].
History of chest pain, palpitation, shortness of breath The presence of systemic microvascular ischemia in these patients can affect cardiac function causing problems with conduction defects and can ultimately leads to cardiac failure[6]
Family history of similer llness, strokes in neonatal period, sudden deaths[3]. In hereditary form there will be a positive family history in between genetically related people[6].
References
  1. AZARM T, SOHRABI A, MOHAJER H, AZARM A. Thrombotic Thrombocytopenic Purpura associated with Clopidogrel: a case report and review of the literature J Res Med Sci [online] 2011 Mar, 16(3):353-357 [viewed 09 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3214346
  2. THORNTON KM, NYP MF, MUSIC APLENC L, JONES GL, CARPENTER SL, GUEST EM, SHAPIRO SM, MANIMTIM WM. An Unusual Case of Rapidly Progressive Hyperbilirubinemia Case Rep Pediatr [online] 2013:284029 [viewed 09 September 2014] Available from: doi:10.1155/2013/284029
  3. TSAI HM. The Kidney in Thrombotic Thrombocytopenic Purpura Minerva Med [online] 2007 Dec, 98(6):731-747 [viewed 09 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2430013
  4. TSAI HM. Thrombotic Thrombocytopenic Purpura: A Thrombotic Disorder Caused by ADAMTS13 Deficiency Hematol Oncol Clin North Am [online] 2007 Aug, 21(4):609-v [viewed 10 September 2014] Available from: doi:10.1016/j.hoc.2007.06.003
  5. TSAI HM. Pathophysiology of thrombotic thrombocytopenic purpura Int J Hematol [online] 2010 Jan, 91(1):1-19 [viewed 10 September 2014] Available from: doi:10.1007/s12185-009-0476-1
  6. BLOMBERY P, SCULLY M. Management of thrombotic thrombocytopenic purpura: current perspectives J Blood Med [online] :15-23 [viewed 10 September 2014] Available from: doi:10.2147/JBM.S46458
  7. VISENTIN GP, LIU CY. 9. Drug Induced Thrombocytopenia Hematol Oncol Clin North Am [online] 2007 Aug, 21(4):685-vi [viewed 13 September 2014] Available from: doi:10.1016/j.hoc.2007.06.005
  8. SEE JR, SABAGH T, BARDE CJ. Thrombotic Thrombocytopenic Purpura: A Case Presenting with Acute Ischemic Colitis Case Rep Hematol [online] 2013:592930 [viewed 13 September 2014] Available from: doi:10.1155/2013/592930

Examination

Fact Explanation
Signs of increase bleeding tendency There will be multiple purpura/ ecchymotic patches and groups of petechiaeand evidence of gum/ nasal bleeding of bleeding from other mucus membranes.Thrombotic Thrombocytopenic Purpura is one of haematological disorder characterized with clotting in small vessels of the body causing reduction in platelet count (thrombocytopenia) causing these signs[1].
Pallor This condition is associated with microangiopathic hemolytic anemia causing red blood cell destruction giving signs of anaemia[1]. Due to the mechanical injury with high shear stress created by microvascular thrombosis is believed to cause fragmentation of red blood cells and hemolysis[3].
Jaundice This is due to the excessive destruction of red blood cells causing jaundice[2].
Fever fever is seem to be occurs in approximately half of the patients[7].
Examination of urine Examination of urine will reveals dark red urine from hemoglobinuria[4]/ haematurea. With microangiopathic hemolytic anemia in which red blood cells are destroyed, free plasma haemoglobin level is increased.This excess hemoglobin filtere by the kidneys and excrete it into the urine, giving urine a dark red color. Haematuria will be present in renal involvement of this condition. Focal and segmental distribution of microthrombi most commonly leads to renal failure[3].
Neurologic examination Neurologic examination reveals alteration in mental status( confusion/ drowsiness), development of seizures, hemiplegia, paresthesias, visual disturbance and aphasia. With focal and segmental distribution of microthrombi, these neurological manifestations can be seen. Trensient ischemic attacks and strokes are common in theses patients[3].
Splenomegaly Splenomegaly may present but organomegaly is not typical[5].
Cardiovascular examination Cardiovascular examination reveals dyspnoic patient, irregular pulse and features of cardiac failure like ankle oedema, gallop rhythm. The presence of systemic microvascular ischemia in these patients can affect cardiac fuction causing conduction defects and these leads finally to cardiac failure[6]
References
  1. AZARM T, SOHRABI A, MOHAJER H, AZARM A. Thrombotic Thrombocytopenic Purpura associated with Clopidogrel: a case report and review of the literature J Res Med Sci [online] 2011 Mar, 16(3):353-357 [viewed 09 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3214346
  2. THORNTON KM, NYP MF, MUSIC APLENC L, JONES GL, CARPENTER SL, GUEST EM, SHAPIRO SM, MANIMTIM WM. An Unusual Case of Rapidly Progressive Hyperbilirubinemia Case Rep Pediatr [online] 2013:284029 [viewed 09 September 2014] Available from: doi:10.1155/2013/284029
  3. TSAI HM. The Kidney in Thrombotic Thrombocytopenic Purpura Minerva Med [online] 2007 Dec, 98(6):731-747 [viewed 09 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2430013
  4. TSAI HM. Thrombotic Thrombocytopenic Purpura: A Thrombotic Disorder Caused by ADAMTS13 Deficiency Hematol Oncol Clin North Am [online] 2007 Aug, 21(4):609-v [viewed 10 September 2014] Available from: doi:10.1016/j.hoc.2007.06.003
  5. KUPERMAN AA, BAIDOUSI A, NASSER M, BRAESTER A, NASSAR F. Microangiopathic Anemia of Acute Brucellosis - is it a True TTP? Mediterr J Hematol Infect Dis [online] , 2(3):e2010031 [viewed 10 September 2014] Available from: doi:10.4084/MJHID.2010.031
  6. BLOMBERY P, SCULLY M. Management of thrombotic thrombocytopenic purpura: current perspectives J Blood Med [online] :15-23 [viewed 10 September 2014] Available from: doi:10.2147/JBM.S46458
  7. RUTKOW IM. Thrombotic thrombocytopenic purpura (TTP) and splenectomy: a current appraisal. Ann Surg [online] 1978 Nov, 188(5):701-705 [viewed 13 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1396769

Differential Diagnoses

Fact Explanation
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 wil 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[1].
Hypertensive emergency In a hypertensive emergency there is elevated blood pressure more than normal value resulting in end organ damage. In this condition central nervous system, cardiovascular system and renal system are commonly involved[2].
Immune Thrombocytopenic Purpura In immune thrombocytopenic purpura there is a immune mediated reduction in circulating platelets which manifests as increase bleeding tendency. So similer to Thrombotic Thrombocytopenic Purpura it is manifest as easy bruising or petechiae. In here intracranial hemorrhages may occur when the platelet count drops to 10 × 109/L[3].
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[4].
Stroke Neurologic manifestations such as alteration in mental status like confusion and drowsiness, seizures, muscle paralysis, paresthesias, visual problems and other cranial nerve involvement is associated with strokes[5].
References
  1. SCHIEFER B, SEARCY G. Disseminated intravascular coagulation and consumption coagulopathy. Can Vet J [online] 1975 Jun, 16(6):151-159 [viewed 10 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1696929
  2. HICKLER RB. "Hypertensive emergency": a useful diagnostic category. Am J Public Health [online] 1988 Jun, 78(6):623-624 [viewed 10 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1350270
  3. 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 10 September 2014] Available from: doi:10.1182/blood-2009-01-129155
  4. TSAI HM. Current Concepts in Thrombotic Thrombocytopenic Purpura Annu Rev Med [online] 2006:419-436 [viewed 10 September 2014] Available from: doi:10.1146/annurev.med.57.061804.084505
  5. NICOL MB, THRIFT AG. Knowledge of Risk Factors and Warning Signs of Stroke Vasc Health Risk Manag [online] 2005 Jun, 1(2):137-147 [viewed 13 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1993942

Investigations - for Diagnosis

Fact Explanation
Full blood count Thrombotic Thrombocytopenic Purpura associated with thrombocytopenia and low haemoglobin levels[1]. If there is any ongoing infection there will be increase in WBC count as well.
Peripheral blood film examination A peripheral blood smear examination will reveals thrombocytopenia and red cell fragmentation(schistocytes) as prominent features[2].
ADAMTS13 activity assay A patient with Thrombotic Thrombocytopenic Purpura due to autoimmune inhibitors of ADAMTS13 typically has very low( less than 10%) ADAMYS13 activity level in their plasma[1].
ADAMTS13-inhibiting antibodies titer Several studies have shown that the presence of inhibitors of ADAMTS13 in most patients are presenting with acute TTP. Inhibitors of ADAMTS13 will persist with fluctuating titers for months to years during periods of clinical remission. With the excessive increase of ADAMTS13 inhibitor titers ADAMTS13 activity will suppress below the threshold level causing relapse of TTP[1].
DNA sequence analysis for mutation of the ADAMTS13 gene Inhibitory antibodies of ADAMTS13 causes a profound deficiency of the protease. according to available data there is more than forty different mutations of the ADAMTS13 gene including mis-senses, non-senses, frame-shifting deletions or insertions, and intronic splicing mutations which are distributed throughout the various domains of ADAMTS13. The majority of these mutations affect the sequence of metalloprotease-spacer domains that are critical for expression of proteolytic activity[1].
Analysis of the VWF multimers In early stage of remission there is an increase in the platelet count which is often coincides with the appearance of ultra large VWF multimers. Because at this stage ADAMTS13 activity remains very low but that is sufficient to ameliorate the binding between VWF and platelet. Ultra large VWF multimers can be seen among patients in remission with persistently low ADAMTS13 activity levels[1].
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[3].
D Dimer In disseminated intravascular coagulation there is elevated levels of D Dimer. This is useful in excluding the differential diagnosis[4].
Computed tomography (CT) scanning and magnetic resonance imaging (MRI) CT scanning or MRI useful in the history or physical findings suggest towards serious internal bleeding or other neurological manifestations to exclude brain ischemia[5].
Renal function tests like serum creatinine, blood urea and Urine full report In Thrombotic Thrombocytopenic Purpura renal involvement is common leading to renal failure. In a case of renal involvement there may be proteinuria with hyaline and granular cases in the urine, elevated serum creatinine levels and blood urea levels. So these tests will useful in screening the renal failure[6] in Thrombotic Thrombocytopenic Purpura and to exclude HUS.
References
  1. TSAI HM. Current Concepts in Thrombotic Thrombocytopenic Purpura Annu Rev Med [online] 2006:419-436 [viewed 10 September 2014] Available from: doi:10.1146/annurev.med.57.061804.084505
  2. ALLFORD S, MACHIN S. Current understanding of the pathophysiology of thrombotic thrombocytopenic purpura J Clin Pathol [online] 2000 Jul, 53(7):497-501 [viewed 10 September 2014] Available from: doi:10.1136/jcp.53.7.497
  3. KIM J, YADAVA M, AN IC, SAYEED A, LAIRD-FICK HS, GOURINENI V, ABELA GS. Coagulopathy and Extremely Elevated PT/INR after Dabigatran Etexilate Use in a Patient with End-Stage Renal Disease Case Rep Med [online] 2013:131395 [viewed 13 September 2014] Available from: doi:10.1155/2013/131395
  4. DURAN I, TANNOCK IF. Disseminated Intravascular Coagulation as the Presenting Sign of Metastatic Prostate Cancer J Gen Intern Med [online] 2006 Nov, 21(11):C6-C8 [viewed 13 September 2014] Available from: doi:10.1111/j.1525-1497.2006.00506.x
  5. ROJAS JC, BANERJEE C, SIDDIQUI F, NOURBAKHSH B, POWELL CM. Pearls & Oy-sters: Acute ischemic stroke caused by atypical thrombotic thrombocytopenic purpura Neurology [online] 2013 May 28, 80(22):e235-e238 [viewed 10 September 2014] Available from: doi:10.1212/WNL.0b013e318294b423
  6. TSAI HM. The Kidney in Thrombotic Thrombocytopenic Purpura Minerva Med [online] 2007 Dec, 98(6):731-747 [viewed 09 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2430013

Investigations - Fitness for Management

Fact Explanation
Full Blood Count Assess the degree of thrombocytopenia and anaemia will helpful in deciding the patients present condition[1].
Computed tomography (CT) scanning and magnetic resonance imaging (MRI) CT scanning or MRI useful in the history or physical findings suggest of serious internal bleeding[2].
Serum troponin level The presence of systemic microvascular ischemia in these patients can affect cardiac fuction causing conduction defects and congestive cardiac failure. In these patient serum troponin level is very important to assess the cardiac status[3].
echocardiogram, electrocardiogram These tests are useful in assessing the cardiac function[4][3].
Blood grouping and cross matching This is useful in management if the transfusion is needed[3].
References
  1. TSAI HM. Current Concepts in Thrombotic Thrombocytopenic Purpura Annu Rev Med [online] 2006:419-436 [viewed 10 September 2014] Available from: doi:10.1146/annurev.med.57.061804.084505
  2. ROJAS JC, BANERJEE C, SIDDIQUI F, NOURBAKHSH B, POWELL CM. Pearls & Oy-sters: Acute ischemic stroke caused by atypical thrombotic thrombocytopenic purpura Neurology [online] 2013 May 28, 80(22):e235-e238 [viewed 10 September 2014] Available from: doi:10.1212/WNL.0b013e318294b423
  3. BLOMBERY P, SCULLY M. Management of thrombotic thrombocytopenic purpura: current perspectives J Blood Med [online] :15-23 [viewed 10 September 2014] Available from: doi:10.2147/JBM.S46458
  4. CHEESMAN M, LEECH G, CHAMBERS J, MONAGHAN M, NIHOYANNOPOULOS P. Central role of echocardiography in the diagnosis and assessment of heart failure Heart [online] 1998 Jul, 80(Suppl 1):S1-S5 [viewed 13 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1766493

Investigations - Followup

Fact Explanation
Full Blood Count This is useful in followup as well to see the level of thrombocytopenia and low haemoglobin level[1].
Reticulocyte count This also useful in follow up[3].
haptoglobin level Due to haemolysis this is useful in routine assessment of patient with newly diagnosed Thrombotic Thrombocytopenic Purpura[3].
Serum LDH level Serum LDH level is usually high in these patients during an acute exacerbation due to tissue necrosis with systemic micro thrombi and haemolysis[2].
Clotting profile with prothrombin time and activated partial thromboplastin time This is useful in excluding any associated clotting factor deficiency[3].
echocardiogram, electrocardiogram These tests are useful in assessing the cardiac function[3].
References
  1. TSAI HM. Current Concepts in Thrombotic Thrombocytopenic Purpura Annu Rev Med [online] 2006:419-436 [viewed 10 September 2014] Available from: doi:10.1146/annurev.med.57.061804.084505
  2. AB RAHMAN WS, ABDULLAH WZ, MUSTAFFA R, AHMED SA, HASSAN MN, HUSIN A. Thrombotic Thrombocytopenic Purpura: Three Peripartum Cases and Diagnostic Challenges Clin Med Insights Case Rep [online] :141-146 [viewed 10 September 2014] Available from: doi:10.4137/CCRep.S12122
  3. BLOMBERY P, SCULLY M. Management of thrombotic thrombocytopenic purpura: current perspectives J Blood Med [online] :15-23 [viewed 10 September 2014] Available from: doi:10.2147/JBM.S46458

Investigations - Screening/Staging

Fact Explanation
Renal function tests like serum creatinine, blood urea and Urine full report In Thrombotic Thrombocytopenic Purpura renal involvement is common, focal and segmental distribution of microthrombi most commonly leads to renal failure. In a case of renal involvement there may be proteinuria with hyaline and granular cases in the urine, elevated serum creatinine levels and blood urea levels. So these tests will useful in screening the renal failure[1].
HIV serology, hepatitis B and C serology, cytomegalovirus serology these infections can precipitate the condition and also due to the treatments these patients are at high risk for getting blood born infections. So during the management screening for these infections are very useful[2].
References
  1. TSAI HM. The Kidney in Thrombotic Thrombocytopenic Purpura Minerva Med [online] 2007 Dec, 98(6):731-747 [viewed 09 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2430013
  2. BLOMBERY P, SCULLY M. Management of thrombotic thrombocytopenic purpura: current perspectives J Blood Med [online] :15-23 [viewed 10 September 2014] Available from: doi:10.2147/JBM.S46458

Management - General Measures

Fact Explanation
Health education Thrombotic Thrombocytopenic Purpura is one of life-threatening haematological disorder causing thrombotic microangiopathy which causes significant morbidity and mortality unless promptly recognized and treated. This is a multi systemic condition and patient should be aware about the condition, symptoms, treatment options complications and prognosis[1].
Antiplatelet agents Low-dose aspirin is given to patients with Thrombotic Thrombocytopenic Purpura (platelet count need to be more than 50 × 109/L). This is given as a supportive care. It is known to improve early survival[1][2].
Antithrombotic therapy As these patients are at high risk of deep venous thrombosis pharmacological DVT prophylaxis with low molecular weight heparin) and nonpharmacological DVT prophylaxis like with graded compression stockings need to be considered[1][3].
Central venous access Central venous lines need to be inserted in to patient with severe thrombocytopenia. This is useful in plasma exchange and it is highly advisable in patients with neurological symptoms or signs of neurological instability. Central venous catheters should be inserted regardless of platelet count[1].
Hepatitis B prophylaxis Patients with previous hepatitis B infection are at risk reactivation following rituximab therapy as it causes B-cell depletion . As prophylaxis antiviral agents need to be considered[1][4].
Folic acid Folic acid need to be given to all patients due to the hemolytic state[1][5].
During pregnancy patient should be treated with methylprednisolone and plasma exchange in a similar way to non pregnant patients This can occur during pregnancy due to the changes in immune regulation or as a precipitation of an episode of symptomatic patient with congenital thrombotic thrombocytopenic purpura. In pregnancy methylprednisolone and plasma exchange can be used in a similar way to nonpregnant patients. But rituximab is not adviced during pregnancy due to risks to the developing fetus.The delivery of the baby does not necessarily in the resolution of the episode[1][6].
Retroviral therapy, plasma exchange and corticosteroids for HIV-associated patients HIV infection is an important cause of this disease. Adequate virological suppression is important.Combined with highly active antiretroviral therapy, plasma exchange and corticosteroid alone (without rituximab) is usually enought to achieve a remission from the acute episode[1].
References
  1. BLOMBERY P, SCULLY M. Management of thrombotic thrombocytopenic purpura: current perspectives J Blood Med [online] :15-23 [viewed 10 September 2014] Available from: doi:10.2147/JBM.S46458
  2. KACICH R, LINKER C. Thrombotic thrombocytopenic purpura. West J Med [online] 1982 Jun, 136(6):513-520 [viewed 13 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1273947
  3. MONAGLE P, CHAN AK, GOLDENBERG NA, ICHORD RN, JOURNEYCAKE JM, NOWAK-GöTTL U, VESELY SK. Antithrombotic Therapy in Neonates and Children: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines Chest [online] 2012 Feb, 141(2 Suppl):e737S-e801S [viewed 13 September 2014] Available from: doi:10.1378/chest.11-2308
  4. TSUTSUMI Y, YAMAMOTO Y, SHIMONO J, OHHIGASHI H, TESHIMA T. Hepatitis B virus reactivation with rituximab-containing regimen World J Hepatol [online] 2013 Nov 27, 5(11):612-620 [viewed 13 September 2014] Available from: doi:10.4254/wjh.v5.i11.612
  5. GRIDLEY TH, WAUGH TR. THROMBOCYTOPENIC PURPURA TREATED WITH FOLIC ACID Can Med Assoc J [online] 1947 Nov, 57(5):487-488 [viewed 13 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1590653
  6. ALQADAH F. Thrombotic thrombocytopenic purpura in pregnancy. Postgrad Med J [online] 1996 Dec, 72(854):768 [viewed 13 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2398665

Management - Specific Treatments

Fact Explanation
Plasma exchange Plasma exchange is the most important acute intervention in Thrombotic Thrombocytopenic Purpura management and this is indicated in all patients with suspected disease. in here both removal of autoantibody by the exchange process (in acquired TTP) as well as supplementation of ADAMTS13 activity in the exchanged plasma[1][2].
Rituximab This anti-CD20 antibody rituximab is a safe and effective treatment for newly diagnosed Thrombotic Thrombocytopenic Purpura. It is use in acute illness and to prevent relapses[1][3].
Corticosteroids Steroids(eg; methylprednisolone) causes rapid immunosuppression and they used initially. Steroids are given intravenously daily for 3 days. The first dose usually administered immediately after the first plasma exchange[1][4].
Other immunosuppressive medication Second-line immunosuppression like mycophenolate mofetil, cyclosporine, and vincristine can be used in rituximab intolerance[1] .
Splenectomy Role of splenectomy in the current management of Thrombotic Thrombocytopenic Purpura is limited as there is little evidence regarding its efficacy and safety. This is done for relapsing disease[1][5].
Recombinant ADAMTS13 Recombinant form of ADAMTS13 helps to achieve higher ADAMTS13 activity[1].
Anti-vWF nanobody This is a bivalent nanobody which is a therapeutic protein derived from the heavy chain variable region of heavy chain. It bind to the N-terminus of the vWF A1 domain and subsequently block its interaction with platelets[1].
N-acetyl cysteine It is having multiple effects including reduction of vWF multimer size and inhibition of platelet aggregation[1].
Novel immunosuppressive agents Other B-cell targeted immunotherapy like Bruton tyrosine kinase inhibitors also known to effective in treatments[1].
References
  1. BLOMBERY P, SCULLY M. Management of thrombotic thrombocytopenic purpura: current perspectives J Blood Med [online] :15-23 [viewed 10 September 2014] Available from: doi:10.2147/JBM.S46458
  2. TOFFELMIRE EB, CLARK WF, CORDY PE, LINTON AL, LOHMANN RC. Plasma exchange in thrombotic thrombocytopenic purpura. Can Med Assoc J [online] 1984 Dec 1, 131(11):1371-1376 [viewed 13 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1483661
  3. YOMTOVIAN R, NIKLINSKI W, SILVER B, SARODE R, TSAI HM. Rituximab for chronic recurring thrombotic thrombocytopenic purpura: a case report and review of the literature Br J Haematol [online] 2004 Mar, 124(6):787-795 [viewed 13 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153075
  4. RUTKOW IM. Thrombotic thrombocytopenic purpura (TTP) and splenectomy: a current appraisal. Ann Surg [online] 1978 Nov, 188(5):701-705 [viewed 13 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC139676
  5. BERNARD RP, BAUMAN AW, SCHWARTZ SI. Splenectomy for thrombotic thrombocytopenic purpura. Ann Surg [online] 1969 Apr, 169(4):616-624 [viewed 13 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1387473