Severe Microangiopathic Hemolytic Anemia Research Articles

A case of hemolytic-uremic syndrome that developed in a 5-year-old child due to acute intestinal infection with hemocolitis

Purpose: to demonstrate a case of hemolytic-uremic syndrome (HUS) in a 5-year-old child associated with an acute intestinal infection of unknown etiology, occurring with hemocolitis. Results. During clinical and laboratory observation, edematous syndrome, oligoanuria, severe microangiopathic hemolytic anemia (decrease in hemoglobin, haptoglobin, increase in Lactate dehydrogenase), thrombocytopenia, consumption coagulopathy, hyperazotemia, acute kidney injury (AKI) according to KDIGO grade 2 (increase in serum creatinine more than 2 times) developed. As part of complex therapy with balanced crystalloid solutions with stimulation of diuresis, it was possible to achieve rapid restoration of diuresis on the 2nd day of hospital stay without the use of renal replacement therapy; he also received antibiotics, anticoagulants, transfusion of fresh frozen plasma and red blood cell suspension. Hyperazotemia was relieved within 5 days, as was thrombocytopenia. The follow-up recovery of renal function showed.

Systemic Lupus Erythematosus Presented by Thrombotic Thrombocytopenic Purpura: A Case Report

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening haematological condition which can be secondary to many disorders. Systemic lupus erythematosus (SLE) can present with thrombotic microangiopathy and the differentiation between them is quite difficult especially in people with no previous history of SLE. Thrombocytopenia and microangiopathic haemolytic anaemia (MAHA) characterized by schistocytes on the peripheral blood smear are the most consistent signs of TTP. Plasma exchange, the main treatment for TTP must be started urgently once the TTP diagnosis is established. We report a case of 20-year-old female with no previous medical problems, who was presented with severe illness and dizziness following tooth extraction and was found to have severe microangiopathic haemolytic anaemia, her platelet count was severely decreased and with subsequent diagnosis as TTP and plasma exchange and steroids were started and fulfilled the European League Against Rheumatism and the American College of Rheumatology 2019 (EULAR/ACR-2019) criteria for SLE. The patient showed satisfactory improvement. This study of case report was made for early diagnosis and immediate treatment of unusual presentation of SLE resulted in a good prognosis.�

Thrombotic Microangiopathy Associated with Pregnancy: Various Outcomes in Different Disorders

Thrombotic microangiopathy (TMA) associated with pregnancy can be fulminant and fatal disorder. Pregnancy outcomes and survival of patients depend on the precise diagnose and appropriate treatment approaches. When a pregnant or postpartum woman presents with sudden and severe microangiopathic hemolytic anemia and thrombocytopenia, conditions that require urgent care must be considered: preeclampsia with severe features (PE/HELLP syndrome), thrombotic thrombocytopenic purpura (TTP), catastrophic antiphospholipid syndrome (CAPS), complement-mediated thrombotic microangiopathy (atypical hemolytic-uremic syndrome, aHUS). The distinction among these syndromes is often unclear because they share multiple clinical features. Overlap between PE/HELLP and TTP, CAPS and aHUS is also apparent from the fact that pregnancy can be a trigger for TMA before and after delivery. These disorders, especially PE imitators, are very important as the causes of maternal and fetal death.Since 2010 we observed 104 patients with pregnancy-associated TMA. Women's age at the time of pregnancy was 32,04±0,83 years old, delivery performed at 34,89±0,74 gestation weeks. The reasons of TMA defined as PE/HELLP in 71 (68,3%) women (main signs: blood pressure more than 160 mm systolic or 110 mm diastolic, platelet count <100 x 10⁹/l and/or abnormal liver function, renal insufficiency, pulmonary edema, cerebral symptoms, eclampsia - generalized seizures, peripartum cardiomyopathy), aHUS- 32 (30,8%), TTP-1 (0,9%) (ADAMTS13 level less than 10%). All of them required preterm operative delivery. Therapeutic plasma exchange (1-9 procedures) performed in 88 (84,6%). ADAMTS13 level assessed before plasma therapy (45-84%, excluding the TTP case), as well as lupus anticoagulant (LA) and antiphospholipid antibodies (APLA) (negative in all patients). In cases of aHUS we use eculizumab in 14/32 (43,75%), but a full course with subsequent successful discontinuation of the drug was received only by one patient. 13/14 patients received 1 to 6 injections of eculizumab.Overall mortality rate was 10 (9,6%), It is noteworthy that only patients with aHUS died- 10/32 (31,25%). Antenatal fetal death occured in 16 (15,4%), among them 12/32 (37,5%) were diagnosed with aHUS. The condition of patients with PE/HELLP improved on 1-3 days after delivery in all cases. In aHUS patients, life-threatening complications persisted and even progressed after delivery: massive uterine bleeding required hysterectomy occurred in 23,2%, acute kidney injury registered in 100% patients, neurological symptoms had 61%, respiratory distress syndrome- 55%, dilated cardiomyopathy- 16,7%. 61,3% required hemodialysis, 51,8%- respiratory care. All of patients who died had 2 “waves” of TMA: first wave has damaged 2-5 organs without any proved infections, but treated with antibacterial combination. Second TMA wave was fatal due to superimposed septic disorders, resistant to antibiotic therapy. Patients on eculizumab treatment had more severe disease at debut with shorter history of aHUS and responded well to eculizumab. Survival of aHUS patients on eculizumab treatment was 71,4%, without it - 64,7%.Therapeutic approaches in TMA associated with pregnancy are different and survival of patients depends on a timely diagnosis. Clinical vigilance requires for early detection of TMA. After that is necessary as soon as possible investigate the ADAMTS13 level to avoid TTP, and LA and APLA to avoid CAPS. Plasma exchange may be first urgent step of treatment in all cases of TMA, but after clarifying the diagnosis therapy should be adjusted. Timely diagnosis and effective approaches including early prescribed targeted therapy in aHUS patients can improve the survival rate and pregnancy outcomes. DisclosuresNo relevant conflicts of interest to declare.

Атипичный гемолитико-уремический синдром и преэклампсия: причина или следствие?

Objective. To study the risk factors for transformation of pre-eclampsia (PE) into atypical hemolytic uremic syndrome (aHUS). Patients and methods. The study included 102 patients with PE, who were divided into two groups. The main group consisted of 59 women with PE and aHUS in the early postpartum period. In the comparison group, there were 43 patients who previously had severe PE, which was not complicated by the development of aHUS. Results. The complications associated with severe PE such as hemorrhage (76.3% vs 48.8%, p = 0.004), placental abruption (33.9% vs 6.9%, p = 0.001), and intrauterine fetal demise (32.2% vs 6.9%, p = 0.002) were significantly more frequent in patients with aHUS compared with the control group. Most of these complications occurred in patients in whom PE lasted more than one week. Also, patients with aHUS had significantly more severe microangiopathic hemolytic anemia (hemoglobin 61.0 [52.5; 73.5] g/L vs 88.0 [73.0; 104.0] g/L, p &lt; 0.001, lactate dehydrogenase 2846.0 [1340.5; 5037.5] IU/L vs 801.0 [497.0; 1269.0] IU/L, p &lt; 0.001), thrombocytopenia (49.5 [31.0; 71.5] K/μL vs 67.0 [43.0; 108.0] K/μL, p = 0.002), hypercreatininemia (424.5 [281.0; 605.0] μmol/L vs 99.0 [86.0; 134.0] μmol/L, p &lt; 0.001) and more severe multiple organ dysfunction syndrome (average number of organ failures – 3.58 vs 1.88, p &lt; 0.001). Among patients with aHUS, complete recovery of renal function was achieved in 42 (71.2%) of 59 women, 9 (15.2%) of 59 women remained on hemodialysis, 8 (13.6%) of 59 women died. In the comparison group, all women showed positive dynamics within 72 hours after childbirth with normalization of all clinical and laboratory parameters. Conclusion. PE itself is a risk factor for the development of aHUS, and patients with severe PE should be considered at high risk for thrombotic microangiopathy. Prolongation of pregnancy in patients with PE increases the risk of developing aHUS by 5 times. Key words: pre-eclampsia, pregnancy-associated atypical hemolytic uremic syndrome, pregnancy, thrombotic microangiopathy, eculizumab

APPROACHING PREGNANCY-ASSOCIATED THROMBOTIC MICROANGIOPATHIES IN THE FACE OF DIAGNOSTIC UNCERTAINTY

SESSION TITLE: Medical Student/Resident Critical Care Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Critical illness is infrequently encountered in pregnant patients though remains a prominent concern due to potential maternal and fetal morbidity and mortality. We report a case of a female in her second trimester with severe microangiopathic hemolytic anemia, thrombocytopenia, and end organ damage to highlight the emergent measures and multidisciplinary action necessary to avoid adverse outcomes when the ultimate diagnosis is not immediately clear. CASE PRESENTATION: A 26-year-old female, gravida 4, para 1, with a medical history of chronic kidney disease due to focal segmental glomerulosclerosis presented at 21 weeks and 2 days gestation with abdominal pain, nausea, and headaches. On initial evaluation the patient was found to have hypertensive emergency, acute kidney injury (AKI), acute liver injury, and intrauterine fetal demise. Within 48 hours of presentation the patient required transfusions for worsening thrombocytopenia and acute anemia with a markedly elevated lactate dehydrogenase (LDH), undetectable haptoglobin and 5% schistocytes. The patient underwent an urgent dilation and evacuation and plasma exchange (PE) for a suspected thrombotic microangiopathy (TMA). She was found to have normal level of ADAMTS13 ruling out thrombotic thrombocytopenic purpura (TTP) and PE was stopped. Cell counts and liver function gradually improved; however, the patient had progression of her AKI with a creatinine peak of 10.9mg/dL one week after initial presentation. Autoimmune and complement studies were obtained revealing a significant elevation in the alternative pathway BB complement level concerning for atypical hemolytic uremic syndrome (aHUS). A renal biopsy was obtained to confirm the presence of TMA. The patient had gradual improvement in renal function and was ultimately discharged with specialty follow up to review the biopsy and make definitive decisions on therapeutic management. Unfortunately the renal biopsy was non-diagnostic due to inadequate tissue sampling and the patient failed to return for outpatient appointments. DISCUSSION: Thrombotic microangiopathies are a rare and devastating group of disorders carrying high morbidity and mortality and pose a diagnostic challenge due to the overlapping clinical and laboratory findings. Pregnancy-specific conditions such as HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome must be differentiated from other causes of TMA including TTP and aHUS. Certain clinical features such as the degree of laboratory derangements and timing during pregnancy may suggest an etiology; however, definite diagnosis often takes several days. CONCLUSIONS: This case demonstrates the necessity for rapid intervention, such as PE for TTP and aHUS, as well as emergent delivery for HELLP Syndrome, even amidst relative diagnostic uncertainty as delay in therapy contributes to worse outcomes. Reference #1: Fakhouri F, Vercel C, Fremeaux-Bacchi V. Obstetric nephrology: AKI and thrombotic microangiopathies in pregnancy. Clin J Am Soc Nephrol. (2012) 7:2100–6. 10.2215/CJN.13121211. 10.2215/CJN.13121211 Reference #2: Gupta M, Feinberg B, Burwick R. Thrombotic microangiopathies of pregnancy: differential diagnosis. Pregnancy Hypertens. (2018) 12:29–34. 10.1016/j.preghy.2018.02.007 Reference #3: Pishko A, Levine L, Cines C, . Thrombocytopenia in pregnancy: diagnosis and approach to management. Blood Rev (2020) 40. 0.1016/j.blre.2019.100638 DISCLOSURES: No relevant relationships by Kelsey Black, source=Web Response No relevant relationships by Megan Conroy, source=Web Response No relevant relationships by Adam Shaver, source=Web Response

Syndromes of thrombotic microangiopathy associated with pregnancy.

When a pregnant or postpartum woman presents with sudden and severe microangiopathic hemolytic anemia (MAHA) and thrombocytopenia, three syndromes that require urgent care must be considered: (1) preeclampsia with severe features/hemolysis, elevated liver function tests, low platelets (PE/HELLP) syndrome; (2) thrombotic thrombocytopenic purpura (TTP); and (3) complement-mediated thrombotic microangiopathy (C-TMA; also referred to as atypical hemolytic-uremic syndrome). The distinction among these three syndromes is often unclear because they share multiple clinical features. Overlap between PE/HELLP syndrome and the other two syndromes is also apparent from the fact that pregnancy can be a trigger for both TTP and C-TMA both before and after delivery and also the increased frequency of PE/HELLP syndrome in women who have recovered from TTP. When diagnostic criteria for PE/HELLP syndrome are present, management of hypertension and delivery is curative. Absence of improvement or actual progression of MAHA, thrombocytopenia, and kidney function abnormalities after delivery requires consideration of TTP and C-TMA. Minimal kidney involvement with severe thrombocytopenia suggests TTP and the need for treatment with plasma exchange; progressive kidney injury (in the absence of a cause for acute tubular necrosis) suggests C-TMA and the need for anti-complement treatment. We describe how we use these criteria to evaluate and manage pregnant/postpartum women with MAHA and thrombocytopenia.

O135. HELLP??? – A case

Introduction HELLP affects about 1% of all pregnancies and up to 20% of pregnant women with severe preeclampsia/eclampsia. Clinical symptoms are typically associated with right upper epigastric pain, headache and visual disturbance. In about 15–20% patients present without hypertension and/or proteinuria. Objectives After delivery symptoms and lab tests of HELLP resolve gradually within 3–4 days, in case of persistent disease awareness for other thrombotic micorangiopathies has to be raised. Methods We present a case of a 26 year old primigravida, who presented in her 35+1 week of gestational age in our labour ward with epigastric pain and starting labour. Further clinical signs (mild hypertension and proteinuria) and her massively deranged lab results suggested severe HELLP with haemolytic anaemia and profound thrombocytopenia (9G/l). After ordering a thrombelastogram (TEG) and short preparation with cortison and blood products an uneventful cesarean section was performed. A healthy boy was born (2480 g/47 cm length; Apgar 7/8/10; umbilical a/v pH 7.29/7.30), but unfortunately his mother’s recovery took an unexpected course, continuing lab tests suggested a thrombotic microangiopathy (TTP/aHUS) and accordingly therapy was started, but nevertheless she died on day 13 after delivery. Results We discuss her disease, management and differential diagnosis in review of the literature. Conclusions In pregnant patients with severe thrombocytopenia and microangiopathic haemolytic anaemia and other symptoms suggesting severe HELLP other thrombotic microangiopathies have to be excluded.

Thrombotic thrombocytopenic purpura or cobalamin deficiency? A case report and review

Introduction: The classic presentation of cobalamin deficiency consists of a macrocytic anemia with or without neurologic manifestations. A common cause of cobalamin deficiency is pernicious anemia, an autoimmune condition in which anti-intrinsic factor antibodies are present. We present a case of pernicious anemia masked by features consistent with thrombotic thrombocytopenic purpura, as well as a review of similar cases in the literature. Case presentation: A 31 year old male presented to the Emergency Department with symptomatic anemia and altered mental status. Laboratory data was significant for microangiopathic hemolytic anemia and thrombocytopenia. A clinical diagnosis of thrombotic thrombocytopenic purpura was made and plasma exchange was initiated. Due to the lack of improvement with plasma exchange, additional laboratory studies were obtained which showed cobalamin deficiency, intrinsic factor antibodies, and ADAMTS13 levels within normal limits. The patient’s clinical and laboratory status improved with parenteral cobalamin replacement and discontinuation of plasma exchange. Discussion: Severe cobalamin deficiency can present as a severe microangiopathic hemolytic anemia that responds rapidly to cobalamin replacement. Key differentiating considerations from thrombotic thrombocytopenic purpura are markedly elevated lactate dehydrogenase, low reticulocyte count, six-lobed polymorphonuclear white blood cells on the peripheral blood smear, and markedly low serum cobalamin.

Catastrophic Antiphospholipid Syndrome with Severe Acute Thrombotic Microangiopathy and Hemorrhagic Complications

The catastrophic antiphospholipid syndrome (CAPS) is a rare life-threatening form of the antiphospholipid syndrome characterized by disseminated vascular thrombosis resulting in multiorgan failure. On an exceedingly rare occasion, CAPS can be associated with severe hemorrhagic manifestations. We report a young woman with a history of several spontaneous miscarriages who presented with menorrhagia and hemoptysis. The patient developed respiratory failure due to diffuse alveolar hemorrhage. Laboratory tests demonstrated severe hemolytic anemia, profound thrombocytopenia, markedly elevated fibrin degradation products, and renal failure. Blood films revealed numerous schistocytes. Serologic tests disclosed hypocomplementemia and autoantibodies directed against several nuclear antigens. Coagulation studies revealed lupus anticoagulant. Echocardiography demonstrated reduced ejection fraction and moderate to severe mitral and tricuspid regurgitation. The patient was diagnosed with CAPS with hemorrhagic manifestations in the setting of new-onset SLE. The patient was treated with hemodialysis, high-dose glucocorticoids, plasma exchange, intravenous cyclophosphamide, and rituximab. Over the ensuing four weeks, the combination therapy led to hematological, cardiopulmonary, and renal recovery. This exceedingly rare case emphasizes that hemorrhagic manifestations, severe microangiopathic hemolytic anemia, and profound thrombocytopenia can dominate the clinical picture in CAPS.

Hemolytic non‐uremic syndrome

We describe three children who developed isolated but severe microangiopathic hemolytic anemia without other manifestations of hemolytic uremic syndrome (HUS) or thrombotic thrombocytopenic purpura (TTP). All three recovered without specific treatment. We propose that they represent a unique phenotype in the spectrum of TTP and HUS, which we term "hemolytic non-uremic syndrome."

Intravenous cyclophosphamide therapy in a case with refractory thrombotic microangiopathic hemolytic anemia and SLE

The case of a 27-year-old woman who simultaneously presented with SLE and severe refractory thrombotic microangiopathic hemolytic anemia (TMHA) is reported. She had extremely high levels of platelet-associated IgG (PAIgG), and her TMHA was refractory to plasma exchange and corticosteroid therapy. However, the TMHA was effectively controlled by i.v. cyclophosphamide therapy. ITP and TTP are generally considered distinct diseases; however, TMHA may occur secondary to platelet aggregation via autoimmune mechanisms in certain cases. Immunosuppressive therapy at an early stage of the disease may be beneficial in refractory cases of TMHA with autoimmune features.

Thrombotic thrombocytopenic purpura: from platelet aggregates to plasma.

Thrombotic thrombocytopenic purpura (TTP) is a syndrome of severe thrombocytopenia and microangiopathic hemolytic anemia without an alternative explanation. Although some patients also have a combination of fever and neurologic and/or renal manifestations, these are not required for the diagnosis. Thus, plasmapheresis should start as soon as TTP is placed high in the differential diagnosis to prevent significant mortality. Histopathologically, TTP is characterized by widespread platelet thrombi in the microcirculation. Ultralarge von Willebrand factor (vWf) multimers found in the patient's plasma are the basis for the platelet thrombi. Recent evidence has linked the abnormal fragments of vWf with deficiency of a plasma enzyme named vWf-cleaving protease, or ADAMTS-13. While a small percentage of patients with TTP have a constitutional defect in this enzyme, many with the acute idiopathic form have an antibody to ADAMTS-13, affecting its ability to cleave vWf. The determination of the enzyme activity and the presence of its inhibitor have emerged as a potential tool in the diagnosis and prognosis of TTP. Furthermore, it helps to differentiate TTP from the hemolytic uremic syndrome, in which the level of ADAMTS-13 is expected to be normal or only slightly decreased.

Hemostatic complications in bone marrow transplantation: a retrospective analysis of 447 patients.

Hemostatic complications are not uncommon after bone marrow transplantation (BMT). However, little is known about the frequency, localization, determinants, and outcome of hemostatic events in autologous and allogeneic BMT. Four hundred forty-seven patients (364 allogeneic, 83 autologous transplants) were evaluated retrospectively for the presence of hemostatic complications (bleeding, thrombosis, hepatic veno-occlusive disease [VOD], microangiopathic hemolytic anemia) from the start of conditioning therapy until June 2000. A total of 83.2% of the patients presented with at least one hemostatic complication during the investigational period. Most bleeding episodes occurred within the first 4 weeks after transplantation and were relatively mild. However, 27.1% of the patients hemorrhaged severely, generally doubling the overall mortality of the BMT recipients. Fatal gastrointestinal or intracerebral hemorrhages contributed to 1.1% of the events. Bleeding was strongly associated with prolonged thrombocytopenia and graft-versus-host disease (GVHD). Hemorrhagic cystitis may additionally have been triggered by the preceding conditioning regimens containing cyclophosphamide. Thromboembolic events occurred most frequently in allogeneic transplant recipients, for whom the incidence was 14.6%. Chronic GVHD and treatment with steroids were the major determining factors. The incidence of hepatic VOD in 4.7% of the allogeneic transplant recipients was associated with a high fatality rate. Busulfan conditioning increased the VOD risk 2.6-fold. Moderate or severe microangiopathic hemolytic anemia was associated with GVHD and occurred in 14.6% of the allogeneic transplant recipients, leading to an increased overall mortality. Hemostatic disturbances, commonly found in the course of transplantation, are associated with a high transplantation risk and closely related to thrombocytopenia and immunologic complications.

Mitomycin-C Nephrotoxicity: A Clinico-Pathologic Study of 17 Cases

The potential nephrotoxicity of Mitomycin-C (MMC) was studied in 17 autopsies from patients treated with this drug, usually in association with other anti-neoplastic agents. Renal functional deterioration was present in seven cases while urinalysis showed an overt proteinuria and hematuria in six and four instances, respectively. Four of these patients also developed a severe microangiopathic hemolytic anemia (MAHA) and thrombopenia. Histological examination did not reveal residual tumor in three of them. However renal lesions similar to those observed in the hemolytic-uremic syndrome (HUS) were associated with glomerular mesangiolytic changes and nuclear atypias in glomerular and tubular cells. Immunofluorescence and ultrastructural studies confirmed these findings. In other patients, variable degrees of cellular atypias and of mesangiolysis were observed. The severity of the glomerular, vascular, and tubular lesions correlated with the total dosage of MMC received. The nephrotoxic potential of MMC seems to be delayed in onset and dose related.

EARLY DIALYSIS AND FRESH FROZEN PLASMA (FFP) IN THE THERAPY OF HEMOLYTIC UREMIC SYNDROME (HUS)

In a 10 week period, 5 children (ages 21 months to 6 years) were seen with characteristic findings of HUS. All 5 presented with bloody diarrhea (3-8 days duration), azotemia (BUN:65-225 and creatinine:4.0-15.1), severe microangiopathic hemolytic anemia (Hgb:4.9-7.4 g%), and thrombocytopenia (platelet count: 13-64,000). Two patients had seizures. Multiple cultures for viruses and bacteria were all negative. Three children were anuric (14, 16 and 21 days) while 2 were severly oliguric (6 and 8 days). All five were treated with peritoneal dialysis from the time of admission and given packed cell transfusions as needed. Administration of FFP was started within the first 30 hours. The time for the platelet count to normalize appeared to vary with the volume of FFP given (0 cc/kg, 8 days; 30 cc/kg, 7 days; 40 cc/kg, 6 days; 66 cc/kg, 72 hours; 78 cc/kg, 48 hours). Neither the amount of FFP given nor the normal platelet count, however, appeared to influence the renal failure or the subsequent recovery of satisfactory renal function. None of the 5 children now require dialysis but 4 of 5 have reduced creatinine clearances (100, 60, 50, 50, 25 cc/minute). The degree of residual renal insufficiency relates well to the length of time these patients were anuric or oliguric (6, 8, 14, 16, and 21 days respectively). These data suggest that vigorous therapy with FFP may ameliorate platelet consumption in HUS and, coupled with early dialysis, be important for a satisfactory outcome.

Microangiopathic haemolytic anaemia in cancer patients with bone marrow infiltration

Eight patients suffering from wide-spread malignancies presented with a severe microangiopathic haemolytic anaemia (MHA) without gross evidence for coagulation abnormalities. The common feature in these patients was bone marrow infiltration with malignant cells, suggesting a pathogenic link between bone marrow carcinosis and red cell destruction. Furthermore, it is concluded that MHA is a rare complication of malignancy and a terminal syndrome rather than an early manifestation of the disease.

Arteriovenous fistula complicating renal transplantation

A case of arteriovenous fistula of the major transplant vessels contributing to posttransplant hypertension and severe microangiopathic hemolytic anemia is reported. Improvement in blood pressure and correction of anemia followed ligation of the fistula. This case reinforces the need for diagnostic evaluation of all patients with sustained post-transplant hypertension.

Microangiopathic haemolytic anaemia associated with hypercalcaemia in an experimental rat tumour.

Summary.A severe microangiopathic haemolytic anaemia develops during the course of tumour growth in rats bearing the solid Walker carcinosarcoma 256. Early changes of blood coagulation are the prolongation of the clotting and clot‐forming time in the thrombelastogram, a reduction of factor‐VIII activity and impaired platelet aggregation. Subsequent decrease of plasma fibrinogen and blood platelets indicate intravascular coagulation as the cause of the haematological changes. Fibrinogen turnover studies with homologous 131I‐fibrinogen showed a significantly shortened half time. Concomitant with the alterations of the clotting mechanism a decrease of plasminogen level as well as an increasingly prolonged euglobulin lysis time were found; these may be interpreted as the result of the fibrinolytic response to intravascular fibrin deposition. Histological examination of the animals’ organs demonstrated fibrin strands and large fibrin thrombi exclusively in the capillaries of the tumour. Simultaneously with the intravascular coagulation syndrome the animals develop a hypercalcaemia caused by a parathyroid hormone‐like substance elaborated by the tumour tissue. Since clinical reports point to an interrelation between thrombotic disorders and hyperpara‐thyroidism, the possible role of hypercalcaemia in triggering intravascular coagulation is briefly reviewed.