Coombs-negative Hemolytic Anemia Research Articles

Acute Hemolytic Anemia as an Initial Presentation of Wilson Disease in Children

Wilson disease (WD) is an inherited disorder of copper metabolism. Hemolytic anemia in WD occurs in up to 17% of patients at some point during their illness. To screen for WD among children presenting with hemolytic anemia. Twenty cases (mean age, 8.8 ± 3.9 y) with Coombs-negative hemolytic anemia, attending the hematology clinic of children hospital, Cairo University, were screened for WD by serum ceruloplasmin level, 24 hours urinary copper before and after D-penicillamine challenge test, and slit-lamp examination for detecting Kayser-Fleischer rings. No case had low ceruloplasmin, whereas bilateral Kayser-Fleischer rings was detected in 5% of our cases. Urinary copper was elevated in 5% before and in 40% after D-penicillamine challenge test. According to the scoring system used, 1 case had definite WD and 7 cases were likely to have WD. These 8 (40%) cases were referred to as group B. Group B had a significantly lower hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin, and reticulocytes (P=0.04, 0.001, 0.04, and 0.04, respectively) and a significantly higher urinary copper after penicillamine (P=0.000) when compared with group A (unlikely WD). WD is not uncommon in children with hemolytic anemia after exclusion of other common causes.

Fulminant Wilson's Disease Managed with Plasmapheresis as a Bridge to Liver Transplant.

New-onset jaundice can be a manifestation of multiple pathologic processes including hemolysis, parenchymal liver disease, and cholestasis; the differential diagnosis is broad and requires a systematic approach. We report a case of a patient who presented with jaundice after starting minocycline for the treatment of acne vulgaris and rapidly developed fulminant liver failure found to be due to Wilson's disease. She also manifested severe Coomb's negative hemolytic anemia and renal failure secondary to hepatorenal syndrome. As a bridge to liver transplant, she was successfully treated with plasmapheresis to decrease serum copper in addition to hemodialysis for acidosis and hyperkalemia. She was able to receive a liver and made a full recovery. The case highlights the use of plasmapheresis as an adjunctive treatment modality in cases of fulminant liver failure due to Wilson's disease.

εGγAγδβ0-Thalassemia

Normal hemoglobin is made of a tetramer of 2 α-globin and 2 β-globin polypeptide chains. Deletions in the β-globin gene cluster can range from a few hundred base pairs to loss of the entire cluster resulting in rare, but clinically significant, thalassemias. One such entity is εGγAγδβ0-thalassemia, a condition that presents within the first few weeks of life as a Coombs-negative hemolytic anemia and is not identified on routine newborn screening or hemoglobin electrophoresis.

Hämatoonkologische Krankheitsbilder

Acquired inhibitors of coagulation cause a life-threatening disease. Clinically newly occurring hemorrhagic diathesis combined with prolonged activated partial thromboplastin time (aPTT) time is diagnostically indicative and can be confirmed by a positive plasma exchange test. For thrombotic thrombocytopenic purpura and hemolytic uremic syndrome (TTP-HUS) the diagnosis of Coombs negative hemolytic anemia together with thrombocytopenia should lead to the detection of fragmentocytes in peripheral blood smears. Hairy cell leukemia is a rare subgroup of chronic B-cell neoplasia with the clinical signs of pancytopenia and splenomegaly which characteristically stain positive for CD103. The gastrointestinal stromal tumor (GIST) has nothing in common with classical soft tissue sarcoma based on the activating mutation of the KIT or PDGFRA gene (positivity for CD117). In all of these disorders the correct diagnosis has a major influence on patient outcome. For the case of acquired inhibitors of coagulation immunosuppressive therapy and substitution of coagulation factors (e.g. recombinant factor VIIa) or for TTP-HUS the immediate start of plasma exchange are mandatory. For hairy cell leukemia a very effective treatment exists with purine analogs (e.g. cladribine) and for metastatic inoperable GIST with tyrosine kinase inhibitors (e.g. imatinib).

Unexplained severe Coombs-negative hemolytic anemia during treatment of refractory chronic lymphocytic leukemia with alemtuzumab

Unexplained severe Coombs-negative hemolytic anemia during treatment of refractory chronic lymphocytic leukemia with alemtuzumab

Index of Suspicion

A 5-year-old previously healthy boy presents to the emergency department (ED) with a 2-week history of intermittent left groin pain, usually occurring later in the day. Pain is not related to eating, movement, urination, or stooling. There is no report of trauma or precipitating event. He screams and refuses to stand up during pain episodes, which occur suddenly and last approximately 1 to 2 hours at a time. He otherwise has normal gait and activity when pain free. He does not wake up at night in pain. No recent illnesses or fevers are reported. Review of systems and his examination findings are unremarkable. Two days prior, he was evaluated in the ED for the same issue and had normal urinalysis, urine culture, and scrotal ultrasonogram results. The consulting urologist did not suspect a urologic process. He was discharged home with pain medication. Today, he returns to the ED because of the intense pain. The patient is admitted for further evaluation and pain management. Complete blood cell (CBC) count, C-reactive protein level, urinalysis results, and plain radiographs of the hips are unremarkable. Computed tomography of the abdomen and pelvis reveals a trace amount of nonspecific free fluid in the pelvis. His pain appears to be alleviated with ibuprofen and bed rest. The following day, he has another episode of intense groin pain after returning from the play room. Physical examination at this time demonstrates only point tenderness on palpation over his symphysis pubis area. No swelling, erythema, or increased warmth was noted in that area. An additional imaging study reveals the diagnosis. A 15-year-old girl presents to the clinic with an itchy rash, fever, headache, nausea, and dizziness. A few days earlier she was evaluated for rash on her back and low-grade fevers. She was prescribed amoxicillin clavulanate for suspected streptococcal …

Overwhelming Paroxysmal Nocturnal Haemoglobinuria in a Patient with Low-Risk Myelodysplastic Syndrome and Long-Term Anticoagulation for Sick Sinus Syndrome

Paroxysmal nocturnal haemoglobinuria (PNH) is a rare form of acquired Coombs negative haemolytic anaemia manifested by the clinical triad of intravascular haemolysis, venous thrombosis and cytopenia. At the molecular level PNH is defined by a clonal expansion of hematopoietic stem cells having undergone somatic mutation of the X-chromosome gene PIG-A. Here we report the case of an 80-year old female patient known for sick sinus syndrome for more than 30 years and low-risk myelodysplastic syndrome (MDS) with uneventful course over the past two years. In good health she underwent her fifth lead replacement under short-term reversal of anticoagulation. Two weeks later she presented at the emergency room for epigastric pain, vomiting and fever. Work up revealed extensive right jugular vein thrombosis, Coombs-negative haemolytic anaemia and acute renal failure. Paroxysmal nocturnal haemoglobinuria was suspected and confirmed by flow cytometric FLAER-assay, which detects clonal deficiency of glycosyl-phosphatidyl-inositol linked surface proteins on monocytes and granulocytes. Thus, search of a PNH clone with FLAER was reliable in the presence of RBC-transfusions and ongoing intravascular haemolysis. Though stabilization of haemolysis was achieved, renal failure progressed and the patient deceased suddenly at the 11th day of hospitalization. Short-term reversal of anticoagulation and functionless retained pacing leads may have catalyzed thrombosis in our MDS patient with a large glycosyl-phosphatidyl-inositol (GPI) deficient clone. In MDS patients under long-term anticoagulation any short-term reversal of anticoagulation for surgical procedures should be preceded by FLAER analysis to uncover an emerging GPI-deficient clone since recent developments in the treatment of this condition allow prevention of intravascular haemolysis and thrombosis by halting the complement cascade at the C5 level with targeted immunotherapy.

Primary Sjögren Syndrome Presenting with Hemolytic Anemia and Pure Red Cell Aplasia Following Delivery due to Coombs-negative Autoimmune Hemolytic Anemia and Hemophagocytosis

A 36-year-old woman presented with hemolytic anemia without a reticulocyte response 38 days after delivery. A marked reduction in erythroid cells and an increase in macrophages with active hemophagocytosis were noted in the bone marrow. While conventional Coombs' tests were negative, the level of red blood cell (RBC)-bound immunoglobulin G (IgG) was increased. The patient was diagnosed with primary Sjögren syndrome (pSS) based on her symptoms, positive anti-SS-A antibodies, Coombs-negative autoimmune hemolytic anemia and pure red cell aplasia associated with RBC-bound IgG and hemophagocytosis. The unique presentation was considered to be a consequence of immunological derangement associated with pSS, pregnancy and delivery.

Successful rituximab treatment for acquired amegakaryocytic thrombocytopenic purpura complicated with Coombs-negative autoimmune hemolytic anemia

Successful rituximab treatment for acquired amegakaryocytic thrombocytopenic purpura complicated with Coombs-negative autoimmune hemolytic anemia

An Unusual Case of Rapidly Progressive Hyperbilirubinemia

We present an unusual case of hyperbilirubinemia with rapid early progression leading to bilirubin encephalopathy in a term neonate. Despite early recognition and intervention, the total serum bilirubin reached a maximum level of 39 mg/dL at 32 hours of life. Prior to an emergent exchange transfusion, the patient's diagnostic evaluation was significant for Coombs-negative microangiopathic hemolytic anemia and thrombocytopenia. Further testing revealed a deficiency of ADAMTS13 protein, or von Willebrand factor-cleaving protease, a finding diagnostic of congenital thrombotic thrombocytopenic purpura, or Upshaw-Schulman syndrome. This rare disease is often misdiagnosed, especially in the newborn period.

What caused hemolytic anemia and colicky abdominal pain? Lead!

What caused hemolytic anemia and colicky abdominal pain? Lead!

Case of Reye's syndrome accompanied by hemolytic anemia and cardiac injury after cytomegalovirus infection

A 6-month-old girl with active human cytomegalovirus (HCMV) infection developed Reye's syndrome after vaccination. She suffered from uncommon complications of HCMV infection, including Coombs-negative hemolytic anemia and cardiac injury, but recovered after the appropriate treatment with prompt ganciclovir and symptomatic support. However, the patient died later as a result of a viral upper respiratory tract infection, which aggravated the primary disease. This case suggests that HCMV infection might be a causative agent of Reye's syndrome.

Cancer-Related Microangiopathic Hemolytic Anemia

Cancer-related microangiopathic hemolytic anemia (CR-MAHA) is a paraneoplastic syndrome characterized by Coombs-negative hemolytic anemia with schistocytes and thrombocytopenia. We reviewed and analyzed all cases of CR-MAHA reported since 1979 (the time of the last published review on this topic) according to predefined criteria. We found 154 cases associated with solid cancer and 14 with lymphoma. Among the solid cancers, gastric, breast, prostate, lung, and cancer of unknown primary (CUP) were most common; 91.8% of cancers were metastatic, and in 19.4% of solid cancers CR-MAHA did not occur until recurrence of cancer. Lymphoma cases included Hodgkin disease, angiotropic lymphoma, diffuse large cell lymphoma, and myeloma. Evaluation of the clinical and laboratory findings revealed that only a minority of cases presented with the features of thrombotic thrombocytopenic purpura (TTP) or atypical hemolytic uremic syndrome (aHUS), with the exception of prostate cancer, where aHUS was a common presentation. Compared to hereditary or immune TTP or aHUS, disseminated intravascular coagulation and pulmonary symptoms were more common in CR-MAHA. Plasma exchange or fresh frozen plasma was rarely effective except in prostate cancer patients with aHUS. CR-MAHA responded to antitumor therapy in many patients with gastric, breast, lung, and CUP cancers. These patients had a superior survival compared to patients without chemotherapy. Compared to the prognosis of patients with metastatic cancer without CR-MAHA, the prognosis of CR-MAHA patients was greatly inferior. There is evidence that some cases of CR-MAHA in lymphoma are immune mediated.

Good response with zinc acetate monotherapy in an adolescent affected by severe Wilson disease

We describe a 17-year-old girl with haemolytic anaemia as presentation of Wilson disease. The diagnosis was based on the findings of < 20 mg/dl ceruloplasmin serum level, Kayser-Fleischer ring and Coombs-negative haemolytic anaemia. Genetic testing revealed the presence of the H1069Q heterozygous mutation. The patient was treated with Zinc acetate monotherapy, with good response, maintened after 22 months. This case emphasizes the importance of recognizing atypical clinical presentation of Wilson disease, which must always be considered in patients with Coombs-negative haemolytic anaemia. The good clinical response to treatment with zinc acetate monotherapy in our case might lend to consider the use of zinc monotherapy as initial therapy also in symptomatic patients with Wilson disease under close clinical observation. Clinical trials are needed to provide evidence for use of zinc monotherapy as first-line therapy in symptomatic patients with Wilson disease.

Progression of double‐hit lymphoma in the midst of R‐hyper CVAD

A 50-year-old female with no medical history presented with B-symptoms for 2 weeks including generalized weakness, fevers, fatigue, and night sweats. Physical exam revealed diffuse cervical and axillary lymphadenopathy with splenomegaly. Initial laboratories showed Coombs-negative hemolytic anemia with agglutination of red blood cells and moderate thrombocytopenia. Some tear drop cells were also seen pointing toward the presence of bone marrow infiltration. Computed tomography (CT) of the body showed a mediastinal mass with widespread lymphadenopathy and splenomegaly. Image 1. Panel A: Right axillary lymph node excisional biopsy showing BCL-2 positivity. Panel B: Right axillary lymph node excisional biopsy showing CD10 positivity. Panel C: Right axillary lymph node excisional biopsy showing follicular low-grade lymphoma. Panel D: Right axillary lymph node excisional biopsy showing low MIB1. Panel E: Mediastinal mass biopsy showing DLBCL with blastoid features. Panel F: Mediastinal mass biopsy showing high MIB1. Panel G: Baseline CT showing a mediastinal mass. Panel H: The mediastinal mass rapidly responded to high dose chemotherapy achieving radiographic complete response after three cycles. Panel I: CT showing recurrence of the mediastinal mass encasing the major thoracic organs.

Coombs Negative Hemolytic Anemia of Unknown Origin in Pregnancy

Background Hemolytic Anemia is very common during pregnancy especially in malaria endemic areas. It often associated with Tropical Splenomegaly Syndrome (now commonly known as Hyper-Reactive Malarial Splenomegay), which is an autoimmune phenomenon that follows episodes of malaria in the past. Very few cases of Coombs Negative Hemolytic Anemia have been reported in literature. This condition has not yet been described in Sub-Saharan Africa; hence we are presenting the first such case.

Reversibility of spur cell anemia

![Figure][1] A 34-year-old patient with end-stage alcoholic liver cirrhosis became increasingly anemic and transfusion-dependent. On admission, he had a Coombs negative hemolytic anemia and a blood smear that showed marked poikilocytosis with numerous spiculated red blood cells (shown, left

Human immunodeficiency virus Associated with Haemophagocytic Syndrome in Pregnancy: A Case Report

Haemophagocytic syndrome (HPS) is a rare condition that has been documented in association with viral, bacterial, fungal and parasitic infections as well as a wide spectrum of malignant neoplasms and autoimmune diseases. Whereas HPS is a known cause of anaemia in HIV infection, its occurrence is uncommon. Its occurrence in pregnancy is even rarer and very few such cases have been reported. Full clinical evaluation and investigations including bone marrow aspiration cytology were done to elucidate the cause of the anaemia. Evaluation revealed severe anaemia, increased serum bilirubin HIV positivity and a low CD4 count. The final diagnosis confirmed the case to be haemophagocytic syndrome in pregnancy. A 31-year-old primigravida presented at 21 weeks of gestation with a two-week history of fever, jaundice and abdominal pain. She responded to treatment. Although a rare condition, this case highlights the importance of a high index of suspicion for the syndrome in HIV positive pregnant women with persistent Coombs negative haemolytic anaemia. Full recovery could be expected following prompt institution of HAART and delivery.

Haemolytic anaemia and abdominal pain – a cause not to be missed

In January 2010, a 39-year-old Sri Lankan man, resident in Switzerland for 15 years, presented to the emergency department with constipation and abdominal pain from which he had suffered intermittently during the previous weeks. On physical examination, the abdomen was soft without tenderness or organomegaly. An abdominal X-ray confirmed stool retention without perforation or bowel obstruction. Laboratory testing revealed a haemoglobin level of 9.1 g dl−1 with normal indices and elevated reticulocytes. The blood film showed poikilocytosis, polychromasia, anisocytosis and basophilic stippling (Figure 1). Liver enzymes, bilirubin and LDH were mildly elevated. Haptoglobin was undetectable and the Coombs test was negative. A blood count performed in 2008 had been unremarkable. The diagnosis of a Coombs negative haemolytic anaemia was made. Despite further investigations, its origin remained unclear: infections, drugs, sickle cells or other haemoglobinopathies, glucose-6-phosphate dehydrogenase or pyruvate kinase deficiency and microangiopathic haemolytic anaemia were ruled out. Because of the abdominal colics, porphyria testing was performed. Increased concentrations of coproporphyrine III, delta-aminolevulinic-acid (urine) and elevated free- and zinc-protoporphyrin (erythrocytes) were observed. These results were not consistent with classical porphyrias because, instead of a single enzyme, a number of enzymes were inhibited. As heavy metals are known to inhibit enzymes such as ALA dehydratase, coproporphyrinogen oxidase and ferrochelatase [1], a blood lead concentration was obtained and found to be 63.2 µg dl−1 (normal < 5 µg dl−1). Reasons for lead exposure such as occupation, food, environment or illicit drugs were not detected. Ceramics with lead-containing glazing were not used in the patient's household and none of the family members had elevated blood lead concentrations. On repeated questioning, the patient admitted having taken five ayurvedic pills per day for 2 months until the end of December 2009 to increase his fertility. The pills had been ordered from India and were labelled ‘ashwagandha/mucuna’, which are sold as aphrodisiacs. Left over pills were examined at the Official Food Law Enforcement Authority, where concentrations up to 7.3 mg of lead per pill and traces of arsenic, chromium and mercury were found. Treatment with the oral heavy metal chelator, dimercaptosuccinic acid (DMSA), was started at a dose of 30 mg kg−1 bodyweight per day for 5 days followed by 20 mg kg−1 for 14 days. After 3 weeks, the blood lead concentration had decreased to 17 µg dl−1; anaemia and red blood cell morphology had normalized and the patient had become asymptomatic. Figure 1 The blood film shows poikilocytosis, polychromasia, anisocytosis and basophilic stippling The majority of cases of adult lead poisoning originate from workplace exposures. Inorganic lead is absorbed from the lungs, especially in adults, or from the gastrointestinal tract, which represents the predominant exposure route in children. Lead from ‘herbal medicines’, especially from Asian countries, is an emerging source of heavy metal poisoning. The blood lead concentration correlated with the symptoms at presentation. Lead concentrations below 50 µg dl−1 may cause symptoms such as asthenia, arthralgia, hypertension, headache and even infertility [2, 3]. Above these concentrations abdominal colics, kidney dysfunction, haemolytic anaemia and encephalopathy may occur. Much of the toxicity of lead can be attributed to interference with calcium-mediated signalling or the distortion of enzymes and structural proteins, in this case leading to symptoms of acute porphyria by impairing enzymes of porphyrinbiosynthesis [1]. Measurement of the blood lead concentration is the mainstay of diagnosis, but careful history taking remains of paramount importance. Basophilic stippling in the blood smear suggests lead intoxication but is non-specific. The key first step in management is to stop exposure. Medical treatment consists of chelation [4, 5] by substances such as DMSA or calcium EDTA. In conclusion, lead poisoning shares symptoms with other conditions and may be easily missed. The importance of a detailed drug history including alternative medicines should be emphasized.

Thrombotic Thrombocytopenic Purpura with Severe ADAMTS-13 Deficiency in a Patient with Antiphospholipid Antibodies and Charcot-Marie-Tooth Disease

A 26-year-old woman with a history of mild mental retardation, Charcot-Marie-Tooth disease (CMT) and idiopathic thrombocytopenic purpura developed severe thrombocytopenia with Coombs-negative hemolytic anemia. Magnetic resonance imaging revealed a fresh cerebral infarction in the left precentral gyrus. ADAMTS-13 deficiency caused by an inhibitor and anti-cardiolipin antibodies were detected in the blood. After treatment with prednisolone and fresh frozen plasma, ADAMTS-13 activity was normalized, the ADAMTS-13 inhibitor had disappeared and the thrombocytopenia with a bleeding tendency was improved. To our knowledge, this is the first case of thrombotic thrombocytopenic purpura caused by ADAMTS-13 deficiency associated with antiphospholipid antibodies and CMT.