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A case of atypical hemolytic uremic syndrome successfully treated with eculizumab.

Thajudeen B, Sussman A, Bracamonte E - Case Rep Nephrol Urol (2013)

Bottom Line: We report a case of aHUS successfully treated with eculizumab.Treatment with eculizumab was initiated which resulted in the stabilization of his hemoglobin, platelets, and LDH.Eculizumab is an effective therapeutic agent in the treatment of aHUS.

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology, University of Arizona, Tucson, Ariz., USA.

ABSTRACT
Atypical hemolytic uremic syndrome (aHUS) is a rare thrombotic microangiopathy (TMA) characterized by the triad of hemolytic anemia, thrombocytopenia, and acute renal failure. Eculizumab, a monoclonal complement C5 antibody which prevents the induction of the terminal complement cascade, has recently emerged as a therapeutic option for aHUS. We report a case of aHUS successfully treated with eculizumab. A 51-year-old male was admitted to the hospital following a mechanical fall. His past medical history was significant for rheumatic valve disease and mitral valve replacement; he was on warfarin for anticoagulation. A computed tomography scan of the head revealed a right-sided subdural hematoma due to coagulopathy resulting from a supratherapeutic international normalized ratio (INR). Following treatment with prothrombin complex concentrate to reverse the INR, urine output dropped and his serum creatinine subsequently increased to 247.52 μmol/l from the admission value of 70.72 μmol/l. Laboratory evaluation was remarkable for hemolytic anemia, thrombocytopenia, elevated lactate dehydrogenase (LDH), low haptoglobin, and low complement C3. A renal biopsy was consistent with TMA, favoring a diagnosis of aHUS. Treatment with eculizumab was initiated which resulted in the stabilization of his hemoglobin, platelets, and LDH. Hemodialysis was terminated after 2.5 months due to improvement in urine output and solute clearance. The interaction between thrombin and complement pathway might be responsible for the pathogenesis of aHUS in this case. Eculizumab is an effective therapeutic agent in the treatment of aHUS. Early targeting of the complement system may modify disease progression and thus treat aHUS more effectively.

No MeSH data available.


Related in: MedlinePlus

Trends in LDH and platelets over time.
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Figure 4: Trends in LDH and platelets over time.

Mentions: A diagnosis of aHUS was made based on biopsy findings, serological data, and clinical history. A normal ADAMTS 13 and an equivocal antibody test to ADAMTS 13 ruled out thrombotic thrombocytopenic purpura. On day 3, hemodialysis was initiated due to anuria and hyperkalemia. Plasma exchange with fresh frozen plasma was initiated on day 5 for treatment of aHUS (60 ml/kg of fresh frozen plasma for restitution). Fresh frozen plasma was selected as the restitution fluid in view of the initial concern about genetic or inherited complement defects. Subsequent quantitative assays looking for genetic or inherited complement defects [factor B 239.7 μg/ml (127.6–278 μg/ml), MCP CD46 positive, factor H 253 μg/ml (160–412 μg/ml) and factor I 33.5 μg/ml (29.3–58.5 μg/ml)] were within normal limits. Factor H antibody was negative. A genetic mutational analysis for the above described complement factors was unable to be performed due to denial from the patient's insurance company. Plasma exchange was discontinued after 2 days, and eculizumab was started after administration of a meningococcal vaccine (day 7). By day 8, the patient's platelets improved to 142 × 109/l and LDH decreased to 945 U/l. Hemoglobin also stabilized. Eculizumab was continued at 900 mg every week for a total of 5 weeks and then transitioned to 1,200 mg every 2 weeks. Urine output gradually improved and hemodialysis was terminated after 2.5 months. His estimated glomerular filtration rate at 6 months was 41 ml/min/1.73 m2 as determined by the MDRD formula. The trends in LDH and platelets over time are represented in fig. 4. A computed tomography scan of the chest/abdomen/pelvis was also done to rule out infection or malignancy as precipitants for aHUS.


A case of atypical hemolytic uremic syndrome successfully treated with eculizumab.

Thajudeen B, Sussman A, Bracamonte E - Case Rep Nephrol Urol (2013)

Trends in LDH and platelets over time.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3924711&req=5

Figure 4: Trends in LDH and platelets over time.
Mentions: A diagnosis of aHUS was made based on biopsy findings, serological data, and clinical history. A normal ADAMTS 13 and an equivocal antibody test to ADAMTS 13 ruled out thrombotic thrombocytopenic purpura. On day 3, hemodialysis was initiated due to anuria and hyperkalemia. Plasma exchange with fresh frozen plasma was initiated on day 5 for treatment of aHUS (60 ml/kg of fresh frozen plasma for restitution). Fresh frozen plasma was selected as the restitution fluid in view of the initial concern about genetic or inherited complement defects. Subsequent quantitative assays looking for genetic or inherited complement defects [factor B 239.7 μg/ml (127.6–278 μg/ml), MCP CD46 positive, factor H 253 μg/ml (160–412 μg/ml) and factor I 33.5 μg/ml (29.3–58.5 μg/ml)] were within normal limits. Factor H antibody was negative. A genetic mutational analysis for the above described complement factors was unable to be performed due to denial from the patient's insurance company. Plasma exchange was discontinued after 2 days, and eculizumab was started after administration of a meningococcal vaccine (day 7). By day 8, the patient's platelets improved to 142 × 109/l and LDH decreased to 945 U/l. Hemoglobin also stabilized. Eculizumab was continued at 900 mg every week for a total of 5 weeks and then transitioned to 1,200 mg every 2 weeks. Urine output gradually improved and hemodialysis was terminated after 2.5 months. His estimated glomerular filtration rate at 6 months was 41 ml/min/1.73 m2 as determined by the MDRD formula. The trends in LDH and platelets over time are represented in fig. 4. A computed tomography scan of the chest/abdomen/pelvis was also done to rule out infection or malignancy as precipitants for aHUS.

Bottom Line: We report a case of aHUS successfully treated with eculizumab.Treatment with eculizumab was initiated which resulted in the stabilization of his hemoglobin, platelets, and LDH.Eculizumab is an effective therapeutic agent in the treatment of aHUS.

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology, University of Arizona, Tucson, Ariz., USA.

ABSTRACT
Atypical hemolytic uremic syndrome (aHUS) is a rare thrombotic microangiopathy (TMA) characterized by the triad of hemolytic anemia, thrombocytopenia, and acute renal failure. Eculizumab, a monoclonal complement C5 antibody which prevents the induction of the terminal complement cascade, has recently emerged as a therapeutic option for aHUS. We report a case of aHUS successfully treated with eculizumab. A 51-year-old male was admitted to the hospital following a mechanical fall. His past medical history was significant for rheumatic valve disease and mitral valve replacement; he was on warfarin for anticoagulation. A computed tomography scan of the head revealed a right-sided subdural hematoma due to coagulopathy resulting from a supratherapeutic international normalized ratio (INR). Following treatment with prothrombin complex concentrate to reverse the INR, urine output dropped and his serum creatinine subsequently increased to 247.52 μmol/l from the admission value of 70.72 μmol/l. Laboratory evaluation was remarkable for hemolytic anemia, thrombocytopenia, elevated lactate dehydrogenase (LDH), low haptoglobin, and low complement C3. A renal biopsy was consistent with TMA, favoring a diagnosis of aHUS. Treatment with eculizumab was initiated which resulted in the stabilization of his hemoglobin, platelets, and LDH. Hemodialysis was terminated after 2.5 months due to improvement in urine output and solute clearance. The interaction between thrombin and complement pathway might be responsible for the pathogenesis of aHUS in this case. Eculizumab is an effective therapeutic agent in the treatment of aHUS. Early targeting of the complement system may modify disease progression and thus treat aHUS more effectively.

No MeSH data available.


Related in: MedlinePlus