Thrombotic Microangiopathic Hemolytic Anemia Research Articles

THROMBOTIC MICROANGIOPATHIC HEMOLYTIC ANEMIA IN SYSTEMIC LUPUS ERYTHEMATOSUS IN A 25 YEARS OLD FEMALE IN CHENNAI, INDIA

Systemic lupus erythematosus (SLE) is an autoimmune condition, affecting multiple organs and tissues by autoantibodies and immune complexes. Hematologic manifestations of SLE include anemia, thrombocytopenia and leukopenia. The most common type of anemia seen in SLE is anemia of chronic disease. Thrombotic microangiopathic hemolytic anemia (TMHA) in SLE is very rare. Incidence of TMHA in children with SLE is common compared to adult cases of SLE. Manifestations of TMHA include presence of schistocytes in the peripheral smear, elevated bilirubin levels, elevated LDH and negative coombs test. This case report focuses on 25-year-old female diagnosed concomitantly with SLE and TMHA, and treated with steroids, blood transfusions, megakaryocyte growth factors and antibiotics.

Hemolytic Uremic Syndrome Caused by Mycoplasma Pneumoniae Infection in Children: A Case Report and Literature Review

We describe the case of a 6-year-old boy with a Mycoplasma pneumoniae (M. pneumoniae) respiratory tract infection associated with thrombotic microangiopathic hemolytic anemia and thrombocytopenia with renal failure which was diagnosed as atypical hemolytic uremic syndrome. Renal biopsy showed features of thrombotic microangiopathy. The patient was treated with azithromycin for the M. pneumoniae infection, and supportive care with red cell transfusion and renal dialysis in the acute period. The microangiopathic hemolytic anemia and thrombocytopenia resolved within 2 months after diagnosis but the renal function damage was irreversible. The patient developed end-stage renal disease and required long term renal replacement therapy.

The effect of emicizumab and bypassing agents in patients with hemophilia – An in vitro study

BackgroundEmicizumab is a nonfactor replacement therapy for hemophilia A (HA) and is a bispecific monoclonal antibody mimicking factor VIII by binding both factors IXa and X. Although it reduces the frequency of bleeding episodes, there is still need for bypassing agents in case of breakthrough bleeds or need for surgery. The HAVEN‐1 study showed an increased risk of thrombotic events and episodes of thrombotic microangiopathic hemolytic anemia with simultaneous treatment with emicizumab and activated prothrombin complex concentrate (aPCC) in high doses (>100 U/kg daily) for more than 1 day, and it is suspected that these drugs have a synergistic hemostatic effect. ObjectivesTo evaluate and compare the hemostatic effect of bypassing agents in vitro in people with HA before and after starting treatment with emicizumab to investigate if dosing should be adjusted to optimize treatment. Patients/MethodsBlood collected before and after start of treatment with emicizumab was spiked with aPCC and recombinant factor VIIa (rFVIIa) at different concentrations. The effect of aPCC and rFVIIa was assessed by thrombin generation assay and thromboelastometry. ResultsSix people with HA were included. The response to aPCC in thrombin generation after starting emicizumab was significantly stronger than before. This synergistic effect was less pronounced for emicizumab and rFVIIa. Furthermore, aPCC shortened thromboelastometry clotting time more effectively after starting emicizumab than before starting this treatment. ConclusionsWe demonstrated a strong synergistic effect of emicizumab and aPCC and a similar but less pronounced effect of rFVIIa in people treated with emicizumab.

Thrombotic microangiopathic hemolytic anemia and complications during pregnancy. To aid the practitioner

Thrombotic microangiopathic hemolytic anemia and complications during pregnancy. To aid the practitioner

Thrombotic Thrombocytopenic Purpura-Hemolytic Uremic Syndrome

Thrombotic Thrombocytopenic Purpura-Hemolytic Uremic Syndrome is an acute illness with abnormalities in multiple organ systems. Patients typically present with thrombotic microangiopathy, thrombocytopenia, and microangiopathic hemolytic anemia without another apparent cause. Additional features include fever, neurologic, and renal abnormalities depending on the site of microangiopathic damage. Potential causes include congenital deficiencies, Shiga-Toxin producing bacteria, numerous drugs, factors related to malignancy, allogeneic hematopoietic cell transplant, cardiovascular surgery, and pregnancy. A medical emergency, appropriate treatment needs to be initiated promptly or the disease can be fatal. Plasma exchange is the initial treatment of choice, but plasma infusion can be used until plasma exchange is available. Adjunctive treatment with glucocorticoids may be used in certain scenarios. If left untreated, the syndrome typically progressively worsens. Affected individuals experience irreversible renal failure, progressive neurological deterioration, cardiac ischemia, and death. With a prompt recognition of the disease and treatment initiation, patients have a better prognosis and mortality rate.

Catastrophic APS in the context of other thrombotic microangiopathies.

The catastrophic antiphospholipid syndrome (CAPS) is a rare disease that affects 1% of cases with antiphospholipid syndrome (APS). CAPS can mimic or overlap with different thrombotic diseases; many patients present with a microthrombotic storm or thrombotic microangiopathic hemolytic anemia (TMHA). Thus, the differential diagnosis of CAPS includes thrombotic thrombocytopenic purpura (TTP), typical and atypical hemolytic uremic syndrome (HUS), systemic infections, malignancies, pregnancy-related disorders, malignant hypertension, heparin-induced thrombocytopenia, and drug-induced thrombotic microangiopathies. Antiphospholipid antibody (aPL) positivity has been proposed as the clue in this differential diagnosis; however, aPL can also occur in healthy people and in those with infections or malignancies. Thus, the differential diagnosis of an aPL-positive patient presenting with a microthrombotic storm is broad; the workup should include a special attention to signs of infection and disseminated malignant disease, assessing the funduscopic signs of malignant hypertension, testing ADAMTS13 activity and anti-heparin-platelet factor 4 (HPF4) antibodies, and searching previous exposure to certain drugs. This article aims to review the main diseases included in the differential diagnosis of CAPS in the context of other thrombotic microangiopathies.

Catastrophic antiphospholipid antibody syndrome in a child with thrombotic microangiopathy

Thrombotic microangiopathic hemolytic anemia (TMHA) is not uncommon in clinical nephrology practice while antiphospholipid syndrome (APS) is uncommon. Although less than 1% of patients with APS develop catastrophic APS (CAPS), its potential lethal outcome because of thrombosis in multiple organs and subsequent multiorgan failure emphasizes its importance in nephrology practice. Here is a case of catastrophic APS in a 7-year-old girl, who presented to us with TMHA associated with antiphospholipid antibodies and subsequently died because of CAPS.

Pulmonary Thrombotic Microangiopathic Hemolytic Anemia Treated Successfully with Anticoagulant Monotherapy

Thrombotic microangiopathic hemolytic anemia (TMHA) caused by antiphospholipid syndrome (APS) is generally associated with renal or neurological complications and plasma exchange is the first line of treatment. We present the case of a 72-year-old woman with APS who had chronic TMHA and pulmonary hypertension without other major complications. TMHA and pulmonary hypertension were refractory to plasma exchange but were treated successfully with anticoagulant monotherapy. Contrast-enhanced computed tomography and perfusion scintigraphy did not detect signs of pulmonary embolism. TMHA localized in pulmonary microvasculature which causes pulmonary hypertension is a very rare complication of APS.

Thrombotic microangiopathic hemolytic anemia in a patient with SLE: diagnostic difficulties

A 19-year-old woman with newly diagnosed systemic lupus erythematosus (SLE) presented with hemolytic anemia, thrombocytopenia, hypertension, tonic-clonic seizures, blurry vision, nephrotic syndrome and renal insufficiency. At a general hospital, the investigations included brain MRI, echocardiography, laboratory tests including measurement of the amount of protein excreted daily, platelet count, levels of lactate dehydrogenase, creatinine and anticardiolipin antibodies, direct Coombs' test, peripheral blood smear, and measurement of blood pressure. At a tertiary institution the investigations included physical examination, electroencephalography, brain MRI, magnetic resonance angiography, repetition of laboratory tests plus measurement of von Willebrand factor-cleaving protease activity, measurement of levels of antibodies to double-stranded DNA and platelets, and renal biopsy. Thrombotic microangiopathic hemolytic anemia with a possible underlying diagnosis of malignant hypertension, antiphospholipid antibody syndrome, catastrophic antiphospholipid antibody syndrome, thrombotic thrombocytopenic purpura, or active SLE. At the general hospital, therapy included a single dose of intravenous cyclophosphamide 500 mg, eight daily plasma exchange treatments, three daily infusions of methylprednisolone 1 g followed by methylprednisolone 60 mg every 8 h, an infusion of rituximab 657 mg and ultrafiltration via hemodialysis. At the tertiary institution, therapy included an infusion of cyclophosphamide 650 mg, aspirin 81 mg daily, prednisone 40 mg daily, mycophenolate mofetil 750 mg twice daily, and aggressive management of hypertension.

Severe limb necrosis: primary thrombotic microangiopathy or “seronegative” catastrophic antiphospholipid syndrome? A diagnostic dilemma

An episode of gastroenteritis triggered severe necrosis of all extremities in a previously asymptomatic male. Hepatic and renal involvement were also manifest, while the hematological picture was one of thrombotic microangiopathic hemolytic anemia. Antiphospholipid antibodies were negative. He responded well to a combination of plasma exchange, anticoagulation (heparin), parenteral steroids, and antibiotics, as well as vasodilators (prostacycline) and hyperbaric oxygen, but died because of a cerebral hemorrhage. The differential diagnosis included thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome, or seronegative catastrophic antiphospholipid (Asherson's) syndrome. The dangers of administering such a combination of therapies with anticoagulation, as well as vasodilatation (prostacycline) and hyperbaric oxygen, are highlighted by the case report and emphasized.

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 microangiopathic hemolytic anemia in systemic lupus erythematosus associated with antiphospholipid antibodies: usefulness of monitoring coagulation–fibrinolysis markers

Thrombotic microangiopathic hemolytic anemia in systemic lupus erythematosus associated with antiphospholipid antibodies: usefulness of monitoring coagulation–fibrinolysis markers

Thrombotic microangiopathic hemolytic anemia in systemic lupus erythematosus associated with antiphospholipid antibodies: usefulness of monitoring coagulation–fibrinolysis markers

Abstract We report on a 24-year-old woman with systemic lupus erythematosus and lupus anticoagulant who developed chronic thrombotic microangiopathic hemolytic anemia. The patient responded well to a combination of plasma exchange and anticoagulant therapy. Changes in the molecular markers for coagulation and fibrinolysis corresponded with the disease activity. We suggest that thrombotic microangiopathic hemolytic anemia should be suspected when anemia and thrombocytopenia of unknown etiologies occur in systemic lupus erythematosus. In such cases, the evaluation of molecular markers for coagulation and fibrinolysis might be helpful both for diagnosis and for assessing the response to therapy.

Thrombotic microangiopathic hemolytic anemia in systemic lupus erythematosus

Thrombotic microangiopathic hemolytic anemia (TMHA) is characterized by thrombocytopenia, microangiopathic hemolytic anemia, fever, neurological symptoms, and kidney involvement. It presents as thrombotic thrombocytopenic purpura (TTP) or hemolytic uremic syndrome (HUS). TMHA has been considered to occur only rarely in systemic lupus erythematosus (SLE). However, there has been an increase in the reporting of this association in recent years, and autopsy studies have suggested that TMHA may be underdiagnosed in SLE because of the similarity in symptoms. We report four patients with SLE-related TMHA and describe 24 more patients from a literature review. All patients were women, 50% had active SLE, 89% presented as TTP, and 11% presented as HUS. Those patients with active SLE had low complement levels. Antiphospholipid antibodies or lupus anticoagulant were positive in 5 of 8 cases. Patients treated with plasma infusions or plasmapheresis had a lower mortality rate at 25% compared with 57% mortality in patients who were not treated with plasma infusions or plasmapheresis. It is suggested that TMHA should be considered in any SLE patient presenting with neurological symptoms or renal failure associated with fever, hemolytic anemia, and thrombocytopenia. Early recognition and appropriate therapy with plasmapheresis may improve prognosis.

Thrombotic thrombocytopenic purpura: a review of the literature with report of a case.

Excerpt Thrombotic thrombocytopenic purpura has become recognized as a clinical entity only in recent years. This uniformly fatal disease, which may affect either sex at any age, is characterized b...