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100 years ago Dr. Eli Moschcowitz described the first case of thrombotic thrombocytopenic purpura. For many decades there were no recognized treatment options, and the mortality rate was extremely high. At the beginning of the 1990 s, therapy with steroids and plasma exchange became increasingly popular, although the mortality rate was still over 20 %. It took until the turn of the millennium for the disease mechanisms (ADAMTS13-deficiency) to be decoded in Bern and New York, thus paving the way for new therapy options. It has now become clear that acquired TTP (iTTP) is an autoimmune disease, and the autoantibodies are directed against ADAMTS13, a protease that cleaves large von-Willebrand multimers. This causes a severe ADAMTS13-deficiency. The ultralarge multimers persist and bind platelets, resulting in microvascular thrombosis. This is distinguished from congenital TTP (cTTP), in which severe ADAMTS13-deficiency is caused by mutations in the ADAMTS13-gene (Upshaw-Schulman syndrome). In other forms of thrombotic microangiopathy (TMA, e. g. aHUS), severe ADAMTS13-deficiency does not occur. Two randomized controlled studies demonstrated the benefit of the selective bivalent anti-von-Willebrand factor (vWF) nanobody Caplacizumab, approved in 2019, in the treatment of iTTP. Various publications from national iTTP cohorts improved the data and showed consistent reductions in the time until platelet normalization, a reduction in refractory courses and exacerbations (especially when therapy is controlled according to ADAMTS13-activity) as well as evidence of reduced mortality. Modern therapeutic options include strategies for preemptive therapy for ADAMTS13-relapse as well as plasma exchange-free treatment. The use of recombinant ADAMTS13 may also expand the therapeutic options in iTTP patients in the future., Competing Interests: Alle Autoren erhielten Honorare für Beratungstätigkeiten, u. a. für die Firma Sanofi. Des Weiteren sind RW, WM, MB, LV, MW, CvA und PB in die Entwicklung der deutschen AWMF-S3-Leitlinie TTP involviert., (Thieme. All rights reserved.)

Thrombotic thrombocytopenic purpura (TTP), which comprises thrombocytopenia, elevated lactate dehydrogenase levels, and anemia in the combination of organ involvement, is a rare but life-threatening condition associated with an extremely high lethality in the acute phase if left untreated. Using the example of a 49-year-old woman admitted to the hospital with unexplained abdominal symptoms and subfebrile temperatures, recommendations for the emergency situation are presented. Increased awareness of the disease and targeted further diagnostics with determination of the PLASMIC score or ADAMTS13 activity may lead directly to diagnosis of TTP; delayed diagnosis is usually associated with secondary complications., (© 2022. The Author(s).)

In the emergency room, patients with anemia and thrombocytopenia are common. Although these findings can often be explained by the medical situation, thrombotic microangiopathy is an important differential diagnosis. In this case, occlusion of the smallest vessels consequently leads to functional impairment of the affected organs. Patients generally present with symptoms of organ dysfunction, e.g., in the kidney or brain. Characteristically, Coombs-negative fragmentation of erythrocytes with hemolysis occurs in the area of the occluded vessels. Lactate dehydrogenase levels are elevated, and platelets and haptoglobin are reduced. Differential diagnoses beyond thrombotic microangiopathy that should be considered are numerous and diverse in their pathophysiology. Rapid workup is needed, because sometimes a specific treatment must be initiated rapidly. For example, thrombotic thrombocytopenic purpura leads to death in about 90% of patients if left untreated. However, by reconstitution of the underlying deficiency of the so-called ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) by plasma separation, survival can be ensured in most cases. Complement-mediated hemolytic uremic syndrome should also be considered and, if suspected, treated with complement inhibition. In many cases, however, thrombotic microangiopathy reflects a disorder elsewhere and may be a manifestation of severe hypertension or a coagulation disorder, such as disseminated intravascular coagulation or antiphospholipid syndrome. It can also be observed as a consequence of drug therapies or metabolic derangement. Systemic workup is therefore necessary for rapid clarification of differential diagnoses., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

CME: Diagnostic Approach and Management of Thrombotic Microangiopathy Abstract. Thrombotic microangiopathies (TMA) are characterized by organ thrombosis induced by endothelial injury. They present with thrombocytopenia, hemolytic anemia and schistocytes. In case of an underlying disease-causing TMA, the treatment of the underlying disease is essential. Primary TMAs are divided into thrombotic thrombocytopenic purpura, hemolytic-uremic syndrome and atypical hemolytic-uremic syndrome. Differentiation of these entities is essential, as fast initiation of empiric treatment might be life-saving and disease-modifying treatments for the different entities do exist.

History: A 42-year-old female patient presented with pyelonephritis. Two days later she complained of hematomas and petechia of the extremities., Diagnosis/clinical Findings: Acquired thrombotic thrombocytopenic purpura was diagnosed. Laboratory result showed a thrombotic microangiopathy and thrombocytopenia of 8 × 10E9/l. ADAMTS13-activity was reported to be reduced and inhibitory antibodies to be present., Therapy and Course: The patient was placed on a therapy with plasma exchange, high-dose steroids, and caplacizumab based on a positive PLASMIC score. Once the diagnosis was confirmed by diminished ADAMTS13-activity and the presence of autoantibodies, rituximab was added. The patient responded well but showed persistently elevated levels of ADAMTS13-autoantibodies, which lead to an extension of Caplacizumab treatment to 58 days., Discussion: Caplacizumab represents a novel effective treatment option for patients with acquired thrombocytopenic purpura. Time to treatment response as well as the risk of relapse were shown to be significantly reduced. However, persistent autoimmune activity can be demonstrated in a significant portion of the patients after the end of treatment putting them at risk for relapses. Thus, careful and frequent surveillance is required., Competing Interests: PTB: Honorare (Vorträge, Advisory Board, Reiseunterstützung) Pfizer, Sanofi Genzyme, Ablynx, AlexionLAV: Honorare (Sanofi Genzyme)FG: Honorare (Advisory Board) Vifor, (© Georg Thieme Verlag KG Stuttgart · New York.)

After circumcision, a young man developed a wound healing disorder. After presenting to our hospital for further wound care, laboratory results showed acute renal failure with hemolytic anemia and thrombocytopenia, which led to the diagnosis of postoperative thrombotic thrombocytopenic purpura (TTP). After therapy with plasma exchange and immunosuppressive therapy with prednisolone and rituximab, the patient recovered with normalization of laboratory results. The TTP is associated with low activity of ADAMTS13 with microvascular platelet aggregation and hemolytic anemia.

Thrombocytopenia is a frequent phenomenon in intensive care medicine. A variety of conditions can be responsible for low platelet counts. As platelets are part of the primary hemostatic system, bleeding is the most important complication of thrombocytopenia. Proper workup of the differential diagnosis to identify the cause of thrombocytopenia is essential because the various underlying disorders require different diagnostic and therapeutic management strategies. A low platelet count is a strong predictor of outcome in critically ill patients.This article summarizes the differential diagnosis and diagnostic workup of thrombocytopenia in the critically ill, describes the most important conditions, and gives an overview on therapeutic options and strategies.

Thrombotic microangiopathy (TMA) is a clinical syndrome that is characterized by hemolysis, thrombocytopenia, and acute kidney injury, known as atypical hemolytic syndrome (aHUS), thrombotic thrombocytopenic purpura (TTP), and shigatoxin-associated HUS (STEC-HUS) among others. Several diseases, like malignoma, infections, malignant hypertension, or autoimmune disease can result in secondary TMAs. aHUS is caused by a hyperactivated complement system. Identification of the underlying causes of the TMA is the most important issue and directly associated with treatment success. In case of secondary TMAs, treatment of the actual disease is the most important step, while in case of complement-mediated HUS treatment of choice is plasma exchange or anticomplement agents. For the treatment of TTP, rapid initiation of plasma exchange or plasma infusion is the treatment of choice. Patients with STEC-HUS should solely receive supportive treatment.

History and Admission Findings: We report on the case of a young women presenting with macrohaematuria, petechiae and strong headaches., Investigations: Laboratory showed a thrombotic microangiopathy with helmet cells, increased LDH levels (>600 U/l), and thrombocytopenia (<40,000/μl)., Diagnosis, Treatment and Course: Due to strong haemolytic activity and headache with blurred vision, immediate plasma separation with fresh frozen plasma was commenced. Markedly decreased ADAMTS13 activity and detection of anti-ADAMTS13 antibodies were consistent with the diagnosis of idiopathic thrombotic thrombocytopenic purpura. In total, 11 plasma separations were required to stop disease activity. In parallel, immunosuppressive therapy using glucocorticoids was initiated. The patient was discharged from the hospital in a good general condition and with normalized laboratory findings 26 days after hospitalization., Conclusions: All patients with anemia and thrombocytopenia should be tested for haemolysis and helmet cells. An early diagnosis and initiation of necessary therapy are determining for the clinical outcome., (© Georg Thieme Verlag KG Stuttgart · New York.)

Multiple trauma during pregnancy is a relatively rare situation which poses a great challenge for the team in charge of treatment. A concomitant disease, such as thrombotic thrombocytopenic purpura (TTP) with thrombocytic coagulopathy increases the complexity of the treatment problems. This article describes the case of a 36-year-old pregnant woman referred to this hospital suffering from multiple trauma with severe liver rupture. Stabilization was achieved after an emergency Caesarean section and packing of the liver. Recurrent massive bleeding from the liver occurred after depacking and was treated successfully with recombinant factor VIIa. The concomitant TTP was treated by transfusion of fresh frozen plasma and corticosteroids. Rapid initiation of therapy was the goal to achieve hemostasis and prevent aggravation of the coagulation disorder and an unfavourable outcome despite severe thrombocytopenia.

Background: Thrombotic thrombocytopenic purpura (TTP) is a severe disease with microthrombi in various organs. The idopathic subtype is characterized by reduced ADAMTS13 activity mediated via autoantibodies against this protease. Induction of autoantibodies mechanistically is incompletely understood, but certain drugs can induce anti-ADAMTS13 antibodies through hapten mechanisms., Case Report: A 56-year-old man was admitted from an external hospital because of a rapidly worsening general condition, hemolytic anemia (hemoglobin 4.17 mmol/l, hematocrit 0.19), and thrombocytopenia (22 Gpt/l) for unknown reasons. Additionally, he was found to have an elevated lactate dehydrogenase (45.37 μmol/l/s). 13 days before hospitalization he had received vaccination against H1N1. Laboratory tests revealed an increased total bilirubin (126 μmol/l), and a decreased haptoglobin level (< 0.08 g/l). The blood smear showed 24% fragmentocytes. Direct and indirect Coombs test were negative. TPP was diagnosed based on the clinical presentation and the detection of ADAMTS13 antibodies. Despite daily plasma exchange via plasmapheresis and administration of corticosteroids, there was no significant rise in platelet counts. Immunosuppression with a total of four weekly doses of rituximab (375 mg/m(2) body surface area) was added. Over the next 5 weeks, the platelet count very slowly rose. After a total of 46 sessions, plasmapheresis was ended with complete remission of the disease., Conclusion: This report emphasizes the immunologic susceptibility of TTP, and suggests the potential, but not proven role of H1N1 vaccination in the pathogenesis of TTP, because no serum before vaccination was available. Severe autoantibody TTP can be successfully treated by administering rituximab in addition to standard treatment with plasmapheresis and corticosteroids.

A 67-year-old male patient with a pancreatic carcinoma and hepatic metastases was admitted with progressive dyspnea and anuria. Previously he had received five cycles of a palliative chemotherapy with gemcitabine and responded well with a reduction of the tumor mass. The laboratory results showed a distinct anemia, thrombocytopenia, an increase in creatinine and lactate dehydrogenase levels. With an additional finding of 21 per mille fragmentocytes in the periphery blood smear, we diagnosed a thrombotic microangiopathy (TMA). Until now the literature lacks well-defined therapy standards for this known but rare condition of gemcitabine. In a few case reports addressing the related microangiopathy of thrombotic thrombocytopenic purpura (TTP), which is characterised by a significant reduction of the von Willebrand factor (vWF) cleaving serum protease ADAMTS-13, encouraging results have been achieved by an immediate plasma exchange. Though ADAMTS-13 activity was not relevantly reduced in our patient, we still observed a rapid improvement of the clinical features as well as of LDH, thrombocytes and fragmentocytes under plasma exchange. The patient was discharged after one month in good clinical condition. Interestingly, during follow-up for further 21 months we found a continued stable status of the pancreatic carcinoma without any cytostatic therapy. In summary, this case provides evidence that the use of plasma exchange therapy in gemcitabine-associated TMA is justified.

Thrombotic microangiopathies are disorders of microvascular occlusion and are characterized by thrombocytopenia and microangiopathic haemolytic anaemia. Varying additional signs and symptoms of organ ischaemia may be present. Thrombotic microangiopathies are pathophysiologically heterogenous disorders and include primarily thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome. Besides this, they may occur in association with certain diseases or drugs, or after allogeneic haematopoietic stem cell transplantation.

For some time now, there have been reports of acral necrosis as a paraneoplasia that may occur in association with a number of different malignant tumours. There have also been a series of reports about acral necrosis associated with chemotherapy with various cytostatics. The treatment of choice if these lesions occur is plasmapheresis. Ultimately, the occurrence of thrombotic microangiopathy (TMA) can only be prevented by close monitoring through regular laboratory controls before each new cycle of chemotherapy. In the differential diagnosis, Raynaud's syndrome should be considered as a premonitory paraneoplasia, a risk factor for the occurrence of acral necrosis in patients with a malignant tumour undergoing chemotherapy, particularly patients with ovarian carcinoma receiving gemcitabine treatment.

Thrombotic thrombocytopenic purpura (TTP) represents a rare complication mainly in the second trimester and can, in its early stage, mimic HELLP syndrome. At 38 weeks of gestation, a 40-year-old primigravida with elevated blood pressure, thrombocytopenia and elevated liver enzymes was diagnosed with HELLP syndrome. Despite a Ceasarean section her laboratory parameters remained pathological with severe thrombocytopenia and hemolysis. In addition, the patient developed neurological comatose-like symptoms. The diagnosis of TTP was made after further tests revealed fragmented red cells in the blood, autoantibodies against ADAMTS13 and a nearly total loss of ADAMST13 plasma activity. The patient fully recovered following repeated plasmapheresis and plasma substitution as well as systemic treatment with dexamethasone. If laboratory parameters do not normalise promptly in spite of the correct treatment for an assumed HELLP syndrome, TTP may be the underlying pathology. As rapid assays for antibodies against ADAMTS13 are not available yet, special consideration must be given to the clinical details in order to make a correct diagnosis.

The chance diagnostic finding of thrombocytopenia occasionally happens during the course of basic laboratory diagnostics (hemogram). This article explains possible differential diagnoses.

Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy. Besides anemia and thrombocytopenia, neurological impairment is common in TTP. A 42-year-old woman was admitted to a department of obstetrics/gynecology because of severe vaginal bleeding due to thrombocytopenia. After platelet transfusion, the patient developed a reduced level of consciousness, confusion, headache, and fever. CT scan did not show pathological changes. Transcranial Doppler sonography revealed increased blood flow velocities of all basal cerebral arteries. Because encephalitis was suspected the patient was transferred to the neurological department. CSF and cerebral magnetic resonance imaging studies were normal. Finally, the detection of schistocytes in the peripheral blood smear and the strong elevation of LDH led to the diagnosis of TTP. After plasma exchange over 3 consecutive days the patient achieved complete remission. The diagnosis was confirmed by laboratory tests (activity of ADAMTS13 <5%, IgG antibodies against ADAMTS13). Platelet transfusion may adversely affect the outcome of patients with suspected TTP. Severely deficient activity of the von Willebrand factor cleaving protease (ADAMTS13) is specific for thrombotic thrombocytopenic purpura.

Background: Thrombotic thrombocytopenic purpura (TTP), in 1924 first described by Moschcowitz, is a clinically heterogeneous syndrome associated with thrombocytopenia, Coombs-negative hemolytic anemia, neurologic changes, renal impairment, and fever. TTP is found after various bacterial or viral infectious diseases, autoimmune diseases and also in association with different drugs., Pathogenesis: After initial endothelial cell injury unusually large von Willebrand factors (vWF) are found in plasma of patients with thrombotic thrombocytopenic purpura. Because of impaired proteolysis these large forms lead to thrombosis of the small vessels. The microangiopathy is followed by mechanical destruction of red cells. In peripheral blood smears these fragmentocytes are important for diagnosis and clinical course., Therapy: The therapy of choice is plasma exchange against fresh frozen plasma, whereupon the mortality could be dramatically reduced in the past decades. In case of treatment resistance to plasma exchange there exists no common treatment schedule. One therapy option is immunosuppressive treatment with corticosteroids and vincristine. In case of chronic relapsing TTP splenectomy should be discussed. In spite of severe thrombocytopenia substitution of thrombocytes is contraindicated.

Background: Only in a few case reports the thrombotic thrombocytopenic purpura was related to ticlopidine with a controversial discussion about this association., Case Report: In a 57-year-old female patient, who was admitted with fluctuating central neurological abnormalities and generalized purpura, was made the diagnosis of a thrombotic thrombocytopenic purpura (TTP, Moschcowitz' syndrome). On admission there were a distinct anemia and thrombocytopenia. Corresponding to the hemolysis the laboratory findings showed raised reticulocytes and elevated LDH with > 900 U/l. The peripheral blood smear showed an enrichment of fragmented red cells (15%) and the bone marrow indicated a hyperplastic erythrocytopoesis and a left shift in megakaryocytopoesis. An increase of eosinophilic granulocytes and the tissue basophilic cells directed to a possible allergic phenomenon of the underlying disease. Until 3 weeks before admission she had been on ticlopidine after a left heart catheter with stenting the left coronary artery 6 weeks earlier. Beside taking of acetylsalicylacid and thyroid hormone there was no other regular medication. An early treatment with fresh frozen plasma and plasmapheresis with plasma exchange with fresh frozen plasma led directly to an elevation of thrombocytes and a normalization of hemolytic parameters., Conclusion: This case demonstrates the possible relationship between thrombotic thrombocytopenic purpura and the administration of ticlopidine.

The 33-year-old woman was violently beaten and suffered from concussion of the upper abdomen. Because of pain she took mefenamic acid for two days. Then she reported hematemesis, melena and vertigo. The value for hemoglobin was determined as 5.8 g/dl. Acute blood loss was suspected, but neither intraabdominal nor upper gastrointestinal hemorrhage could be detected. Further investigations revealed a Coombs-negative hemolytic anemia and thrombocytopenia, and microangiopathic hemolysis was suggested by the detection of fragmentocytes in a peripheral blood smear. The diagnosis of thrombotic thrombocytopenic purpura (TTP) was made, though the patient did not suffer from manifestations of impaired microcirculation like neurological symptoms or renal failure. The TTP was found to be associated with HIV infection. The hematological disease responded well to the treatment with fresh-frozen plasma.

Background: According to recent research, the hemolytic-uremic syndrome (HUS) and thrombotic-thrombocytopenic purpura (TTP) are variable expressions of the same entity (HUS-TTP) with a common pathomechanism (endothelial cell damage, microthrombi) and common treatment (plasma infusion, plasmapheresis). The condition is still serious with a poor prognosis, and the therapeutic regimen is not yet standardized (cryosupernatant and factor VIII free plasma, steroids, immunoglobulins, anticoagulation, dextrane, prostacyclin, vincristine, splenectomy?)., Clinical Observations and Review of the Literature: Over an observation period of 15 years we considered the differential diagnosis of HUS-TTP in 34 patients, and treated 11 patients with 12 clinical courses specifically with fresh-frozen plasma (plasmapheresis was additionally performed in 10 of them). The 12 courses were retrospectively evaluated and compared with results achieved in the literature. The mean age of the patients was 43 years (+/- 14), and 9 of the 11 patients were women (2 courses given to one woman). The hemolysis improved in 9 of 12 courses, the cerebral manifestation in 3 of 4 cases, and the thrombocytopenia in 2 of 4 cases. Renal failure responded in only 4 of 9 cases and the response was delayed in these patients. Three patients died: one of brain edema due to TTP-specific cerebral microangiopathy and two due to the underlying disease (lupus erythematosus, mixed connective tissue disease)., Conclusion: Treatment of HUS-TTP is started with fresh-frozen plasma infusions (1-1.5 liters/day), but plasmapheresis should be added 2 days later (3 x 4 liters/week, whereby 2 liters should be given as fresh-frozen plasma). The administration of fresh-frozen plasma must be continued every day. In resistant cases, specific therapy should not be terminated before 4 weeks.

For centuries it has been the dream of many physicians to cure illnesses by eliminating disease provoking substances which are thought to circulate in the human body. Technical developments during the past 20 years have made therapeutic plasma exchange (TP) a useful procedure for clinical application. Because of the lack of well controlled studies the true benefit of the method remains speculative in many clinical situations. Since the report of the American Medical Association (AMA) Panel on Therapeutic Plasmapheresis in 1985 several controlled studies on this subject have been published in recent literature; they are reviewed in this article. In summary, TP seems justified only in some area and well defined situations such as thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, acute and severe myasthenia gravis, severe Guillain-Barré-syndrome, hyperviscosity syndromes such as hyper- and paraproteinemia, and in several intoxications and metabolic disorders such as Refsum disease or hereditary hyperlipidemia type IIa.

Idiopathic thrombocytopenic purpura characterised by an increased bleeding tendency is a well-known clinical entity in childhood. From 1983 to 1992 68 patients suffering from ITP were treated at the Children's Hospital of the Medical Academy of Magdeburg. 11 patients with mild or without clinical symptoms and platelet counts of more than 20 Gpt/l did not receive any treatment; all children recovered spontaneously. 38 patients with severe haemorrhagic manifestations and thrombocytes less than 20 Gpt/l were treated with corticosteroids and had a sustained remission. 10 patients who had responded to corticosteroids initially and subsequently relapsed were given other treatments (Anti-Rhesus-antibodies, HDIVG). All patients achieved a continuous remission. A chronic disease was observed in 8 patients; 3 of them were splenectomised. One child died due to massive gastrointestinal bleeding.

A 50-year-old man complained of lumbar pains, lack of energy, dysarthria and ataxic gait. Investigation revealed progressive anaemia (haemoglobin initially 10.5 g/dl, later 6.8 g/dl) and thrombocytopenia (initially 67,000/microliters, later 25,000/microliters). In addition he had unexplained pyrexia of up to 39.8 degrees C. Lactate dehydrogenase was 780 U/l and fragmented red cells were noted in the blood film. Because of suspicion of thrombotic thrombocytopenic purpura, treatment with fresh plasma by infusion was immediately initiated. On the third day of treatment he developed left ventricular failure; auscultation revealed a blowing early diastolic murmur over Erb's point together with a spindle-shaped early diastolic murmur over the right second intercostal space. Computed tomography of the skull showed recent haemorrhage into the left half of the cerebellum and an older right posterior infarct. The abdominal ultrasound scan suggested a haemorrhagic spleen infarct. In view of these findings the diagnosis was revised to embolizing aortic endocarditis with aortic reflux (confirmed by colour Doppler echo-cardiography). Aortic valve replacement was performed immediately, and the patient was treated with gentamycin 80 mg/d and teicoplanin 400 mg/d for four weeks. Postoperatively he was given 12 units of platelet concentrate and the platelet count remained stable thereafter (greater than 100,000/microliters). Splenectomy became necessary because the splenic haematoma increased in size during oral anticoagulant therapy. After a 6 week hospital stay the patient was discharged in good condition.

The managing of the pregnant patient with immune thrombocytopenic purpura (ITP) is complicated by the unavailability of the foetal platelet count and the risk of bleeding. We report on our experiences of 17 pregnancies in 15 patients, who delivered in the Department of Gynaecology of Freiburg University from 1969 to 1989 (frequency: 0.5 per 1,000). ITP was established prior to pregnancy in 9 of 15 patients, and developed in 6 cases during pregnancy. The a patients received steroid therapy ante partum. However, maternal platelet count did not relate to infant platelet count. Eleven infants were born vaginally, six by caesarean section. One of the 17 live births died immediately post partum at the 28th week of gestation. Six infants were temporarily thrombocytopenic at delivery without further morbidity. Based on our experience and the literature, an individual management of delivery for parturient patients with ITP is recommended.

In a 29-year-old man with primary thrombotic-thrombocytopenic purpura a significantly increased plasma concentration of platelet-specific proteins was demonstrated as an expression of increased intravascular platelet activation and destruction during the acute phase of the disease. There was also abnormally elevated IgG loading of platelets. During administration of fresh plasma alone (total of six litres over one week) the clinical state deteriorated further into coma and failure of spontaneous ventilation. The marked thrombocytopenia and microangiopathic haemolytic anaemia remained unchanged. Only after repeated plasmapheresis was it possible to break through the acute disease process. Remission (restoration of vital functions, normalization of platelet count and haemolysis signs) was achieved after five courses of plasmapheresis with a total exchange volume of 20 litres. At least in this case, the therapeutic success of plasmapheresis argues for an immunological-toxic genesis of thrombotic-thrombocytopenic purpura.

Plasma exchange (PE) is the treatment of choice in emergencies arising in patients suffering from the hyperviscosity syndrome, factor VIII antibody haemophilia, autoimmune haemolytic anaemia or post-transfusion purpura. Apart from these clear indications, the efficacy of PE in other hematological disorders such as thrombotic thrombocytopenic purpura, immune thrombocytopenia, cryoglobulinaemia, rhesus incompatibility, autoimmune cytopenia and AB0 incompatibility with bone-marrow transplantation is less well defined. In such disorders PE can be performed when conventional treatment has failed.

Case history of a patient is reported who developed signs of preeclampsia in 28th week of her first gravidity. Within one day severe haemolysis and diffuse haemorrhage occurred and an emergency section was performed. Subsequently, supported respiration became necessary because of diffuse infiltrations of the lung. Laboratory data then were conclusive for a thrombotic thrombocytopenic purpura (Moschcowitz's disease) and therefore the patient was subjected to plasma exchange during seven days: this measure induced rapid and full clinical and laboratory remission. The case history is discussed on the background of the pertinent literature and the special perspective of a pathophysiological identity between the two syndromes: HELLP (haemolysis, elevated liver enzymes, low platelets) and Moschcowitz's disease (thrombotic thrombocytopenic purpura); this seems to be of special interest for an adequate therapy by plasma exchange.

Thrombotic thrombocytopenic purpura (TTP) is an uncommon disorder which usually occurs in young adults. It is characterized by a pentad of clinical findings: fever, neurological abnormalities, renal dysfunction, microangiopathic hemolytic anemia and thrombocytopenia. The histological hallmark is the presence of platelet thrombi occluding the microcirculation of multiple organs. The etiology and pathogenesis of disseminated platelet aggregation are uncertain and obviously not uniform in individual patients. Experimental findings suggest that microthrombi may result from intravascular platelet activation or form secondarily at sites of vessel wall damage. The differential diagnosis of TTP includes the hemolytic uremic syndrome in which the microangiopathic changes are exclusively found in the kidneys. When untreated, TTP invariably runs a progressive and fatal course. In recent years, prognosis has been improved by new forms of therapy such as plasmapheresis or infusions of fresh frozen plasma which may lead to recovery in about 80% of patients.

Report on 5 patients with thrombotic thrombocytopenic purpura. Four of the five survived. The following forms of treatment have been used: up to 1976, splenectomy and corticosteroids; since 1976, antiplatelet agents and exchange transfusions, and since 1978, antiplatelet agents and fresh plasma or plasma exchange. The author's experience is identical to that in the more recent case reports: early treatment with antiplatelet agents and fresh plasma-in case of failure with plasma exchange - appears to improve the hitherto fatal prognosis.

Thrombotic thrombocytopenic purpura (TTP) and the hemolytic uremic syndrome (HUS) have in common a microangiopathic hemolytic anemia involving disseminated platelet aggregation and endothelial damage of the microvasculature mainly of the brain (TTP) and kidney (HUS). The underlying pathomechanism still remains unclear. The disease takes an acute, dramatic and frequently fatal course. Unfortunately a broadly approved therapeutic regimen is still lacking since the rarity of TTP and HUS makes study of a large group of patients impossible. We have observed and treated 14 patients with TTP and HUS during a period of 9 years. Most of the cases have been triggered by infectious diseases and pregnancy. Diagnostic cornerstones were hemolytic anemia, schistocytes on peripheral blood smears and consumption thrombocytopenia. Renal and cerebral symptoms were observed regularly, whereas lesions of the pancreas, liver and heart were much less frequent. The treatment included plasma transfusion (47%), plasma exchange (42%), high dose corticosteroids (74%), antiplatelet agents (53%), vitamin E (32%) and vincristin (11%). The outcome of 19 episodes of TTP or HUS was as follows: in 78% complete recovery, in 11% persistence of impaired renal function, and in 11% death. From analysis of our cases it is concluded that plasma transfusions and high dose corticosteroids improve the prognosis of TTP and HUS significantly.

In addition to the typical manifestations of thrombotic-thrombocytopenic purpura like thrombocytopenia, haemolysis, fever, coma and renal failure, signs of a beginning DIC could be seen in a patient after abdominal surgery. Haemostatic, cardiovascular and respiratory data are presented. Pulmonary angiography by using a Swan-Ganz-catheter revealed multiple filling defects reversible with therapy. Treatment with fresh whole blood aggravated thrombocytopenia. Daily infusions of fresh frozen plasma combined with heparinisation and antithrombin III because of DIC, induced haematologic remission. Renal failure and cerebral symptoms could not be influenced. Diagnosis, monitoring and therapy are discussed.