Microangiopathic Haemolytic Anaemia and Experimental Tumour-Cell Emboli

S ummary . The mechanism by which disseminated carcinoma may induce microangiopathic haemolytic anaemia has been studied in rats using intravenous injections of Walker carcinosarcoma-256 cells. Following the injection of tumour cells there was sequestration of radio-labelled fibrinogen and platelets in the lungs and a simultaneous fall in peripheral platelet count and rise in free plasma haemoglobin. Anti-fibrinolytic treatment (EACA) and triamcinolone accentuated the changes whereas heparin abolished the effect. Electron microscopy demonstrated fibrin and platelet deposition around tumour cells. It is concluded that intravascular coagulation around tumour cell emboli is an important mechanism in the production of microangiopathic haemolytic anaemia in disseminated carcinoma.     

Microangiopathic hemolytic anemia

It is reported on a more infrequent or too little regarded clinical picture within the form circle of the disseminated intravasal coagulation disturbances, the microangiopathic haemolytic anaemia (MHA). Diagnostically heuristic is the clinical triad haemolytic anaemia, thrombocytopenia and haemorrhagic diathesis. The microangiopathic haemolytic anaemia is described on the basis of a casuistics, the present knowledge about pathogenesis and therapy are discussed.     

Fibrinogen Catabolism in Microangiopathic Haemolytic Anaemia

S ummary . Fibrinogen catabolism has been studied in six patients with microangiopathic haemolytic anaemia, three patients with fragmentary haemolytic anaemia following the insertion of valve prostheses into the heart and ten control patients. Increased rates of catabolism of ¹³¹ I-fibrinogen were found in the patients with microangiopathic haemolytic anaemia. Evidence of enhanced fibrinolysis was not present.
This finding suggests that intravascular coagulation is a feature of some cases of microangiopathic haemolytic anaemia and supports the hypothesis that the interaction of red cells with fibrin may result in the characteristic morphological appearances in these cases.     

Disseminated prostatic carcinoma presenting with acute interstitial nephritis and microangiopathic haemolytic anaemia

Abstract A 74-year-old man with metastatic prostatic carcinoma developed acute oliguric renal failure, a microangiopathic haemolytic anaemia and thrombocytopaenia. A renal biopsy showed an acute interstitial nephritis but no changes suggestive of the haemolytic uraemic syndrome. He recovered normal renal function after treatment with haemodialysis and prednisone 20 mg daily for five days. Previous assumptions about the renal lesion in patients with malignancy-associated microangiopathic haemolytic anaemia may need review.     

Observations on the Mechanism of the Haematological Changes in the Haemolytic Uraemic Syndrome of Infancy

S ummary . The haemolytic uraemic syndrome of infancy (HUSI) is one of a group of diseases described by Brain, Dacie and Hourihane under the generic name 'microangiopathic haemolytic anaemia' (MHA). Survival studies using labelled red cells support the concept that increased haemolysis results from damage to the red cells sustained in small blood vessels. Studies with labelled platelets and fibrinogen fail to provide evidence for continuing intrarenal coagulation once the classic triad of haemolytic anaemia, thrombocytopenia and renal failure has been established.     

Microembolism Syndrome: Acute Respiratory Failure and Disseminated Intravascular Coagulation

Summary: Haematological studies were performed in thirteen patients with acute respiratory failure secondary to trauma (10 cases), or other causes in which clinical features suggesting disseminated intravascular coagulation were present including shock, haemorrhagic manifestations and central nervous system, renal, endocrine and hepatic dysfunction. In the four fatal cases features of intravascular clotting shown at autopsy included focal haemorrhages, thrombi and infarcts.
Thrombocytopenia, decreased factor II levels and elevated fibrin split products were observed in all patients. Levels of other coagulation factors varied but serial changes followed a pattern characteristic of disseminated intravascular coagulation. Ten patients had low levels of plasminogen initially. Serial thrombin times were not greatly prolonged and euglobulin lysis times were lengthened. Red cell fragmentation and progressive anaemia in all cases, combined with either a decrease in haptoglobin or a rise in plasma haemoglobin in nine patients, provided evidence of microangiopathic haemolysis. β ₁A-globulin (C'3) was sub-normal in nine of twelve patients studied.
These data demonstrate disseminated intravascular coagulation leading to secondary fibrinolysis, microangiopathic haemolysis and, apparently, complement activation. In the light of both clinical and experimental observations, disseminated intravascular coagulation is an important pathogenic mechanism in acute respiratory failure of diverse aetiologies, and explains many of its features.     

Thrombotic thrombocytopenic purpura mimicking an acute meningoencephalitis

Thrombotic thrombocytopenic purpura is a rare, threatening disease characterized by thrombocytopenia, microangiopathic haemolytic anaemia and organ dysfunction, e.g., neurological impairment and renal insufficiency. We describe a patient with neurological impairment mimicking a meningoencephalitis in whom a thorough clinical evaluation along with appropriate laboratory tests led us to identify an underlying thrombotic thrombocytopenic purpura. The successful outcome of this patient was based on plasma exchange and immunosuppressive treatment. Thrombotic thrombocytopenic purpura should be considered in the differential diagnosis of patients presenting with any neurological abnormalities, anaemia and unexplained thrombocytopenia.     

Thrombotic microangiopathy and renal failure associated with antineoplastic chemotherapy

Five patients with carcinoma developed thrombotic microangiopathy (characterized by renal insufficiency, microangiopathic hemolytic anemia, and usually thrombocytopenia) after treatment with cisplatin, bleomycin, and a vinca alkaloid. One patient had thrombotic thrombocytopenic purpura, three the hemolytic-uremic syndrome, and one an apparent forme fruste of one of these disorders. Histologic examination of the renal tissue showed evidence of intravascular coagulation, primarily affecting the small arteries, arterioles, and glomeruli. Because each patient was tumor-free or had only a small tumor at the onset of this syndrome, the thrombotic microangiopathy may have been induced by chemotherapy. Diagnosis of this potentially fatal complication may be delayed or missed if renal tissue or the peripheral blood smear is not examined, because renal failure may be ascribed to cisplatin nephrotoxicity and the anemia and thrombocytopenia to drug-induced bone marrow suppression.     

A case of thrombotic thrombocytopenic purpura following allogeneic bone marrow transplantation

A case of thrombotic thrombocytopenic purpura (TTP) is reported in a 40-year-old man 6 months after allogeneic bone marrow transplantation for multiple myeloma. The features of TTP included microangiopathic haemolytic anaemia, severe thrombocytopenia, fluctuating neurological abnormalities, and progressive renal impairment. Despite treatment with anti-platelet agents, prostacyclin infusion, intensive immunosuppression and prolonged plasma exchange, the patient developed end-stage renal failure and is now on maintenance haemodialysis 18 months after the onset of TTP. Graft-versus-host disease and cytomegalovirus infection could not be implicated as aetiological factors, and cyclosporin medication had ceased 1 week before the clinical onset of his disease. The unusually intensive pre-transplant chemotherapy and radiotherapy protocol used in this patient appear to be most likely cause of the generalized endothelial damage resulting in TTP in this patient.     

How I treat thrombotic thrombocytopenic purpura and atypical haemolytic uraemic syndrome

Thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uraemic syndrome (aHUS) are acute, rare life‐threatening thrombotic microangiopathies that require rapid diagnosis and treatment. They are defined by microangiopathic haemolytic anaemia and thrombocytopenia, with renal involvement primarily in aHUS and neurological and cardiological sequelae in TTP. Prompt treatment for most cases of both conditions is with plasma exchange initially and monoclonal therapy (rituximab in TTP and eculizumab in aHUS) as the mainstay of therapy. Here we discuss the diagnosis and therapy for both disorders.     

Microangiopathic Haemolytic Anaemia Associated with Hypercakaemia in an Experimental Rat Tumour

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.     

The Significance of Microangiopathic Haemolytic Anaemia in Accelerated Hypertension

S ummary . Twenty-two patients with accelerated hypertension and varying degrees of renal involvement have been studied in order to assess the significance of microangiopathic haemolytic anaemia (MAHA) and the possible pathogenic role of intravascular fibrin deposition in this condition. Vascular damage was assessed by retinal photography including fluorescein angiography. Haematological investigations including examination of peripheral films and assessment of red cell fragmentation were carried out. Fibrinogen catabolism was measured using radio-iodine labelled fibrinogen.
No correlation between the degree of vascular damage in the retinal vessels and the blood pressure, degree of red cell fragmentation or evidence of renal damage was found. There was a significant increase in red cell fragmentation when the creatinine clearance was 20 ml/min or less. Fibrinogen derivatives were demonstrated in the serum in the minority and in the urine of the majority of those patients with MAHA. Fibrinogen catabolism was normal in all cases.
The significance of microangiopathic haemolytic anaemia in accelerated hypertension is discussed. It is suggested from these data that the red cell fragmentation occurs predominantly within the kidney and that there is no evidence that fibrinogen deposition plays an important role in red cell damage, or that it is an important pathogenic factor in producing accelerated hypertension.     

Cytomegalovirus-induced thrombocytopenia and haemolysis in an immunocompetent adult

We describe a patient with severe symptomatic thrombocytopenia and haemolytic anaemia caused by cytomegalovirus (CMV) infection. As far as we know, this is the second case in the literature. Treatment with ganciclovir seemed to be more effective for thrombocytopenia than treatment with corticosteroids. The hypothetical mechanisms leading to thrombocytopenia and haemolysis in CMV infection are briefly discussed. In cases of acute thrombocytopenia and clinical manifestations of an infectious disease, with or without haemolysis, testing for CMV may be useful in connection with therapeutic consequences.     

Cytomegalovirus-induced thrombocytopenia and haemolysis in an immunocompetent adult

We describe a patient with severe symptomatic thrombocytopenia and haemolytic anaemia caused by cytomegalovirus (CMV) infection. As far as we know, this is the second case in the literature. Treatment with ganciclovir seemed to be more effective for thrombocytopenia than treatment with corticosteroids. The hypothetical mechanisms leading to thrombocytopenia and haemolysis in CMV infection are briefly discussed. In cases of acute thrombocytopenia and clinical manifestations of an infectious disease, with or without haemolysis, testing for CMV may be useful in connection with therapeutic consequences.     

Severe hemolysis complicated by renal insufficiency in a patient with mitro-aortic bioprostheses and review of the literature

The authors report a very rare case of massive haemolytic anaemia complicated by renal failure in a patient with a double aortic and mitral bioprosthesis. The haemolysis was attributed to degeneration of the aortic bioprosthesis causing turbulent flow, aggravated by associated infectious endocarditis. The essential condition for haemolysis is a change in blood flow through the valve by degeneration or other associated pathology. The haemolytic anaemia completely regressed after aortic valve replacement as did the renal failure.     

Severe thrombopenias during heparin therapy. A phenomenon of intra-vascular platelet aggregation

Haemorrhage or thromboembolism during heparin therapy are usually attributed to a prescribing error. However, these clinical manifestations--especially thromboembolism--may occur with heparin therapy during severe thrombocytopenia. The authors describe the clinical, biological and physiopathological features characterising this thrombocytopenia with reference to 7 personal cases and a review of the literature. The incidence of heparin-induced thrombocytopenia varies between 0.5 and 1%. It seems to be more common (4%) during heparin therapy for thromboembolic disease. The thrombocytopenia appears 8 days after the onset of heparin therapy. It is characterised by the high incidence of thromboembolism (70% of cases) compared to haemorrhagic phenomena (10% of cases). Thrombocytopenia is asymptomatic in 20% of cases. The thrombocytopenia is peripheral, i.e. the bone marrow is normal, and isolated, i.e. there are no deficiencies in the factors of coagulation. One of our cases was of special interest because it was complicated by disseminated intravascular coagulation. Eight cases of disseminated intravascular coagulation have previously been reported. Analysis of platelet aggregation demonstrates the relationship between heparin and thrombocytopenia. Mixing the plasma of patients with thrombocytopenia and plasma rich in platelets in the presence of heparin lead to thrombo-agglutination. In contrast, in control and non-thrombocytopenic heparinised subjects, no reaction was found. These observations prove the existence of a platelet aggregant factor in the plasma during thrombocytopenia. This disappears 6 weeks to 2 months after stopping heparin. This platelet aggregant factor initiates platelet aggregation which is responsible for thrombocytopenia and for the initiation of phenomena of coagulation, so explaining the thromboembolic phenomena.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prevalence,patterns of disease and outcome in patients with systemic lupus erythematosus who develop severe haematological problems

OBJECTIVE: To evaluate the prevalence of major haemolytic disease-severe autoimmune haemolytic anaemia and severe thrombocytopenia-and to assess when these features develop. We also sought to analyse the clinical and serological outcomes of patients with haemolytic anaemia and thrombocytopenia with systemic lupus erythematosus (SLE) as compared with patients without these cytopenias. METHODS: We reviewed retrospectively all the available case notes from our lupus cohort of 305 patients followed up between 1978 and 2000 (mean follow-up 7 yr). We identified 30 patients with SLE (9.8%), of whom 20 (6.6%) had severe haemolytic anaemia and 10 (3.3%) had severe thrombocytopenia. Each patient was matched for age, sex and ethnicity with two control patients. RESULTS: We recorded a total of 42 episodes of severe haematological events: four patients had a second haemolytic episode and eight patients had a second thrombocytopenic episode. Five patients had both thrombocytopenia and haemolytic anaemia. One per cent of patients had severe haemolytic anaemia prior to the diagnosis of SLE and 2.5% of patients presented with these haematological disorders. Haemolytic anaemia and thrombocytopenia were associated with renal involvement (0.01>P>0.001) and anticardiolipin antibodies (ACL) (0.01>P>0.001), but not anti-dsDNA antibodies. Calculation of the BILAG index at the time of severe haematological crisis demonstrated that renal, central nervous system involvement and general symptoms are more frequently present. Forty-one per cent of patients were already on either prednisolone (<10 mg) or an immunosuppressive agent at the onset of the event. CONCLUSION: Our data demonstrate that both haemolytic anaemia and thrombocytopenia are associated with ACL but not anti-dsDNA antibodies. When faced with a patient with a severe haematological manifestation of lupus, active disease in other organs is likely to be present.     

Severe reversible autoimmune haemolytic anaemia and thrombocytopenia associated with diclofenac therapy

Severe immune haemolytic anaemia and thrombocytopenia developed in a 71-year-old female within 10 d of starting diclofenac (Voltarol) therapy. These complications resolved within 3 weeks of discontinuation of the drug and corticosteroid therapy. A warm autoantibody of the IgG type together with C3 was found in the direct antiglobulin test of the patient's RBC. The patient's serum and RBC eluate contained a warm autoantibody which reacted with all commercial panel cells without the addition of diclofenac, and gave a negative reaction with Rh null and -D- RBC. This pattern of interactions is similar to haemolysis associated with alpha-methyldopa, indicating the presence of autoantibodies directed against structural components common to all Rh antigens. The coexistence of immune thrombocytopenia and immune haemolytic anaemia is suggestive of an autoimmune disease caused by modified T-cell regulation. Although immune haemolytic anaemia is a rare complication of diclofenac therapy, our observations illustrate the severity of haemolytic anaemia in the occasional patient and stress the need for increased awareness of such a development.     

Dilantin-induced disseminated intravascular coagulation with purpura fulminans. A case report.

A patient developed disseminated intravascular coagulation with purpura fulminans 1 month after starting Dilantin therapy for a seizure disorder. In addition, the patient developed exfoliative dermatitis, hepatitis, cutaneous vasculitis, and microangiopathic hemolytic anemia. She was successfully treated with adrenal steroids and heparin for her purpura fulminans. The hepatitic dermatologic, along with hemorrhagic, complications of Dilantin are reviewed, and the possible origin of the vasculitis and disseminated intravascular coagulation is discussed.     

Haemolytic anaemia as initial manifestation of wilson's disease

Summary Common manifestations of Wilson's disease are disorders of the liver and brain. A rare complication of this inherited disease is acute intravascular haemolytic anaemia. We report the case of a 33-year old female patient who was admitted to the hospital with acute haemolysis as the initial symptom of Wilson's disease. The haemolysis preceded the definitive diagnosis by 20 months. It is concluded that in any case of unclear haemolytic anaemia, especially in adolescents or in young adults, Wilson's disease should be considered.