β+-thalassemia

CASE REPORT

Multiorgan Failure During a Sickle Cell Crisis in Sickle/␤ⴙ-Thalassemia Fasika M. Tedla, MD, and Eli A. Friedman, MD ● In contrast to the chronic nephropathy associated with sickle cell syndromes, acute renal failure and multiorgan dysfunction caused by acute sickling crisis are encountered infrequently. The authors present the first case of extensive multiorgan failure during a sickling episode in a patient with sickle/␤ⴙthalassemia. The authors also review the interaction of the thalassemias with sickle cell disease and outline the distinctive course of their patient in comparison with previous reports. Am J Kidney Dis 42:E4. © 2003 by the National Kidney Foundation, Inc. INDEX WORDS: Acute renal failure (ARF); sickle cell crisis; ␤ⴙ-thalassemia; multiorgan failure; sickling crisis; hyperviscosity syndrome.

A

N INDOLENT progressive chronic nephropathy is well documented in sickle cell disease (SCD).1 Acute renal failure (ARF), however, is infrequent during the course of SCD, and, when detected, has been attributed to a depleted plasma volume or rhabdomyolysis.2 Several reports of multiorgan failure in SCD have included ARF.3-5 While acute painful episodes are known to occur in sickle/␤⫹-thalassemia (ST),6 acute multiorgan failure has not been reported. We present the first report to our knowledge of multiorgan failure associated with ARF in ST. CASE PRESENTATION A 22-year-old black man with ST presented with severe left hip pain for 7 days and right knee pain for 1 day with unremarkable physical findings except for mild tenderness in his left hip. He was admitted for a painful crisis affecting his left shoulder a month before his current admission. Avascular necrosis afflicted his left and then right femoral head in 1997 and 1999, respectively. On admission, his leukocyte count corrected for nucleated red blood cells (NRBCs) was 7,823/mm3, his hemoglobin was 10.6 g/dL (106 g/L), and his platelet count was 413,000/ mm3. Numerous sickle cells were noted on the peripheral film. Plasma electrolytes were normal, the blood urea nitrogen level was 6 mg/dL (2.14 mmol/L), and the serum creatinine level was 0.7 mg/dL (61.9 ␮mol/L). A chest x-ray showed minimal cardiomegaly. Treatment consisted of intravenous fluid repletion and analgesics. On the third day after admission, the patient became lethargic and anuric. At that time, hydromorphone was discontinued after a total dose of 30 mg over 72 hours. He remained afebrile and normotensive but had abdominal pain and paraparesis along with diffuse abdominal tenderness and absent bowel sounds. Muscle power was III/V in muscle groups of the lower extremities. Pain and temperature sensations were lost below the knee, and position sense was lost in the feet. No sensory level was apparent. His leukocyte count

corrected for NRBCs increased to 18,583/mm3, and his hemoglobin decreased to 8.6 g/dL (86 g/L), whereas the platelets fell to 138,000/mm3. Blood cultures remained negative. On arterial blood gas measurement, his pH was 7.31, his partial pressure of oxygen was 82 mm Hg, and his partial pressure of carbon dioxide was 18 mm Hg while receiving oxygen at a flow rate of 2 L per minute by nasal cannula. Consultation for hemodialysis was requested for rises in serum potassium to 7.2 mEq/L (7.2 mmol/L) and serum creatinine to 5.3 mg/dL (468.5 ␮mol/L). Perturbed liver function was indicated by elevated aspartate transaminase of 12,857 U/L, alanine transaminase of 8095 U/L, and a raised alkaline phosphatase of 194 U/L. Total bilirubin increased from 2.6 mg/dL (44.5 ␮mol/L) on admission to 10.6 mg/dL (181.3 ␮mol/L). Direct bilirubin was 8.9 mg/dL (152.2 ␮mol/L). The prothrombin time was 26.6 seconds with an international normalized ratio (INR) of 4.3, and the partial thromboplastin time was 41.8 seconds (reference, 23.6 to 36 seconds). His peak creatine kinase was 3,240 U/L. Serum amylase level was 1,439 U/L, and lipase was 2,684 U/L. A new left lower lobe infiltrate appeared on the chest x-ray. Ultrasonography showed normal-sized kidneys. The initial diagnostic possibilities of spinal cord compression, infarction, or cauda equina syndrome entertained by the neurologic and neurosurgical consultants were excluded by magnetic resonant imaging of the lumbosacral spine, which only showed increased vertebral T2 signals consistent with bony infarcts. On the fourth hospital day, subsiding abdominal pain and

From the Department of Medicine, State University of New York Health Science Center at Brooklyn, Brooklyn, NY. Received November 14, 2002; accepted in revised form April 21, 2003. Address reprint requests to Fasika M. Tedla, MD, Clinical Assistant Instructor, Department of Medicine, State University of New York Health Science Center at Brooklyn, 450 Clarkson Ave, Box 52, Brooklyn, NY 11203. E-mail: [email protected] © 2003 by the National Kidney Foundation, Inc. 0272-6386/03/4202-0022$30.00/0 doi:10.1016/S0272-6386(03)00666-8

American Journal of Kidney Diseases, Vol 42, No 2 (August), 2003: E4

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TEDLA AND FRIEDMAN Table 1.

Study

Reports of Multiorgan Dysfunction in Sickle Cell Syndromes

Hemoglobin Type

Hassel et al3 Geigel and Francis4

Hemoglobin S (10), Hemoglobin S–Hemoglobin C (SC)(4) Hemoglobin S

Bolan˜os-Meade et al5

Hemoglobin S

decreased levels of liver enzymes, serum amylase, and serum lipase indicated improvement. Concurrently, muscle strength in the lower extremities improved. Urine output remained below 300 mL over 24 hours. Hemodialysis was started and repeated for a total of 5 dialyses until the 14th hospital day when diuresis (urine output 3 L/d) and a return of the serum creatinine to 1.4 mg/dL (123.8 ␮mol/L) were noted. The percentage of hemoglobin S decreased from 55 to 45 after transfusion of 2 units and exchange transfusion of 1 unit of packed erythrocytes.

DISCUSSION

Notable in the clinical features of the case we present, in addition to the extent of organ involvement, is the absence of obvious precipitating factors for sickling. There was no focus of infection identified, nor were there episodes of significant hypoxia. A peak creatine kinase of 3240 U/L argues against rhabdomyolysis contributing significantly to his renal failure. Although the effect of myoglobin on renal function also depends on the coexistence of other nephrotoxic insults, there is evidence to suggest that the level of creatine kinase predicts the risk of developing renal failure, with ARF occurring usually at values much higher than that observed in our patient.7,8 Vaso-occlusive phenomena are the major source of morbidity in patients suffering from sickle cell disease. Most patients present with painful episodes9 often in association with an underlying infection. Whereas a number of factors have been identified to influence the degree of sickling, the 3 most important factors are the levels of deoxyhemoglobin, hemoglobin S, and hemoglobin F in the erythrocyte.10 Both ␣- and ␤-thalassemia generally tend to ameliorate the clinical and hematologic manifestations of sicklecell disease.11,12 However, the clinical spectrum of ST varies based on the levels of hemoglobin S and hemoglobin A; those with higher hemoglobin S and lower hemoglobin A concentrations have a course indistinguishable from severe

No. of Cases

14 1 1

Organs Involved

Lungs, kidneys, liver, skeletal muscle Central nervous system, kidneys, liver Kidneys, central nervous system

No. of Deaths

1 0 1

sickle-cell disease.12,13 This is particularly true of patients with sickle/␤o thalassemia disease. Table 1 shows the number of subjects, type of hemoglobinopathy, pattern of organ involvement, and outcome of patients reported. Hassel et al3 reported on 14 patients with 17 episodes of multiorgan failure involving the respiratory, hepatic, and renal systems and rhabdomyolysis. They defined the acute multiorgan failure syndrome in sickle cell disease as the development of severe dysfunction of at least 2 of 3 major organs in the setting of a sickle cell pain episode. ARF developed in 13 episodes of their series, of which 3 patients required hemodialysis. The only death in the series was related to respiratory failure. All patients responded to simple or exchange transfusion. In other reports4,5 the clinical picture resembled that of thrombotic thrombocytopenic purpura, and the patients showed dramatic response to plasma exchange. ARF variably has been defined in terms of the degree of elevation of serum creatinine level or as loss of renal function requiring dialysis. An increase in serum creatinine level of ⱖ0.5 mg/dL from baseline or an increase by 50% of baseline values is used commonly to diagnose ARF. Although prerenal causes account for the majority of cases of ARF, hospital-acquired ARF is frequently caused by more than one mechanism of injury. Prognosis in ARF largely depends on the cause and overall status of the patient. In general, nonoliguric renal failure portends a better prognosis than oliguric renal failure, largely as a reflection of the severity of the underlying insult. Despite maximal supportive care, mortality in the setting of multiorgan failure ranges from 50% to 80%.14 The pathophysiology of acute multiorgan failure syndrome in sickle cell crisis is unclear. However, the rapid reversal of the syndrome

MULTIORGAN FAILURE DURING A SICKLE CELL CRISIS

with simple or exchange transfusion of packed erythrocytes indicates that it is caused by widespread microvascular occlusion by irreversibly sickled red cells. In the report by Hassell et al,3 a high hemoglobin level was identified as a common denominator. The median hemoglobin level in patients with homozygous hemoglobin S (SS) disease was 9.3 g/dL (93 g/L) compared with 13.2 g/dL (132 g/L) in those with hemoglobin S – hemoglobin C (SC) disease. Our patient, with a hemoglobin level of 10.6 g/dL (106 g/L), appears to be another example of their observation that a relatively higher hemoglobin level occurred in those patients with multiorgan failure. Our patient had a more extensive involvement of organs than previously described. The remarkable recovery of his renal function and the function of other organ systems suggests that the renal lesion in our patient was acute tubular necrosis caused by microthrombosis of the renal vasculature. The overall course of our patient extends the scope of understanding of ST and supports utilization of vigorous dialytic therapy and exchange transfusion in the presence of concurrent renal, hepatic, neurologic, and pancreatic malfunction with rhabdomyolysis. REFERENCES 1. Sabrio P, Scheinman JI: Sickle cell nephropathy. J Am Soc Nephrol 10:187-192, 1999 2. Sklar AH, Perez JC, Harp RJ, Caruana RJ: Acute renal

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failure in sickle cell anemia. Int J Artif Organs 13:347-351, 1990 3. Hassel KL, Eckman JR, Lane PA: Acute multiorgan failure syndrome: A potentially catastrophic complication of severe sickle cell pain episodes. Am J Med 96:155-162, 1994 4. Geigel EJ, Francis CW: Reversal of multiorgan system dysfunction in sickle cell disease with plasma exchange. Acta Anaesthesiol Scand 41:647-650, 1997 5. Bolan˜os-Meade J, Keung YK, Lo´pez-Arvizu C, Florendo R, Cobos E: Thrombotic thrombocytopenic purpura in a patient with sickle cell crisis. Ann Hematol 78:558-559, 1999 6. Green M, Hall RJ, Huntsman RG, Lawson A, Peason TC, Wheeler PC: Sickle cell crisis treated by exchange transfusion. Treatment of two patients with heterozygous sickle cell syndrome. JAMA 231:948-950, 1975 7. Shieh SD, Lin YF, Lu KC, et al: Role of creatine phosphokinase in predicting acute renal failure in hypocalcemic exertional heat stroke. Am J Nephrol 12:252-258, 1992 8. Ward MM: Factors predictive of acute renal failure in rhabdomyolysis. Arch Intern Med 148:1553-1557, 1988 9. Embury SH: Sickle cell anemia and associated hemoglobinopathies, in Goldman (ed): Cecil Textbook of Medicine (ed 21). Philadelphia, PA, Saunders, 2000, p 897 10. Bunn HF: Pathogenesis of sickle cell disease. N Engl J Med 337:762-769, 1997 11. Higgs DR, Aldridge BE, Lamb J, et al: The interaction of alpha-thalassemia and homozygous sickle-cell disease. N Engl J Med 306:1441-1446, 1982 12. Serjeant GR, Ashcroft MT, Sergeant BE, Milner PF: The clinical features of sickle-cell/␤-thalassemia in Jamaica. Br J Haematol 24:19-30, 1973 13. Olivieri NF: The ␤-thalassemias. N Engl J Med 341:99-109, 1999 14. Thadhani R, Pascual M, Bonventre JV: Acute renal failure. N Engl J Med 334:1448-1460, 1996