Pulmonary embolism and splenic infarction in a patient with sickle cell trait

A 43 year-old black man with sickle cell trait documented by hemoglobin electrophoresis presented with severe pleuritic chest pain and hypoxemia three weeks after discharge following abdominal surgery. A pulmonary embolus was diagnosed by angiography and he was treated with heparin; the minimum arterial pO2 was 55 torr while O2 was being administered at a rate of 3 L/min. During this therapy, he developed abdominal pain. Computerized tomography suggested splenic infarction, which was documented by radionuclide liver-spleen scan and magnetic resonance imaging (MRI); the patient's spleen had been normal at exploratory laparotomy three weeks previously. No source for emboli was identified in the deep venous system by MRI. Although splenic infarction has been reported in patients with sickle cell trait at high altitude, this is the first reported case of splenic infarction secondary to the hypoxemia of pulmonary embolism in a patient with sickle cell trait. The spleen is subject to infarction in sickle cell trait because blood flow is slow through a hypoxemic and acidemic environment. The additional hypoxemia due to pulmonary embolism is presumed, in our patient, to have created a local splenic environment which permitted infarction to occur.     

Splenic infarction associated with sickle cell trait at low altitude

Abstract

Objective and importance

Sickle cell trait is widely known to be associated with splenic infarction at high altitudes. Although textbooks and reviews imply that this complication does not occur at low altitudes, we encountered such a case and identified several previous cases in the literature.

Clinical presentation

An 18-year-old woman with sickle cell trait who resided near sea level presented with left upper quadrant abdominal pain and was found to have multiple splenic infarcts. She was otherwise well, with no comorbidities that would predispose to hypoxemia or vascular injury. A review of the literature revealed 12 previously published cases of low-altitude splenic infarction in patients with sickle trait; 7 of those patients had comorbidities that likely predisposed to splenic infarction.

Intervention

None.

Conclusion

Spontaneous splenic infarction can occur in patients with sickle trait who live at low altitudes. It is unclear whether this complication is rare, or whether it is relatively common but under-recognized.     

Acute splenic sequestration crises in adults with sickle cell disease

Reports of acute splenic sequestration crises in adults with sickle cell hemoglobin C disease or sickle cell thalassemia are rare, although an enlarged and distensible spleen persists in half of these patients. Seven episodes of acute splenic sequestration crises in four adults, two with sickle C disease and two with sickle thalassemia, are described. The crises were life-threatening and recurrent in all, but there were no fatalities. One patient had mild steady-state thrombocytopenia suggesting hypersplenism. Technetium 99m/sulfur colloid scanning of the spleen during the acute splenic sequestration crises in three patients showed almost total lack of splenic uptake or decreased uptake with intrasplenic filling defects thought to be splenic infarcts or hematomas on follow-up computed tomographic scanning. The scanning abnormalities resolved following recovery from the crises. Acute splenic sequestration crises probably are common in adults with sickle C disease and sickle thalassemia but may be underdiagnosed or misdiagnosed as splenic infarctions. The hematologic and splenic findings during acute splenic sequestration crises resemble those following splenic vein ligation in animals.     

Interaction of sickle cell trait with hereditary spherocytosis: splenic infarcts and sequestration

The association of sickle cell trait (SCT) and hereditary spherocytosis (HS) has been reported in only 18 patients. Three of these 18 patients experienced splenic infarct or acute splenic sequestration. We report here a 46-year-old African-American male, the oldest reported case to date, who experienced episodes of hemolysis and severe left upper quadrant pain for the past 26 years. The patient had compensated hemolysis with splenomegaly. A CT scan of the abdomen revealed a large infarct in the spleen. The diagnosis of SCT was confirmed with isoelectric focusing, cation exchange and reverse-phase HPLC. The presence of a silent, interacting globin variant as the cause of hemolysis and sickling in the spleen was ruled out by sequencing of the alpha1-, alpha2- and beta-globin genes. The diagnosis of HS was established by an osmotic fragility test. The interaction of HS and SCT leads to RBC dehydration with increased MCHC and intracellular Hb S concentration presumably favoring intrasplenic sickling and resultant splenic infarcts and sequestration as seen in this case.     

Massive splenic infarction in Saudi patients with sickle cell anemia: a unique manifestation

Splenic infarcts are common in patients with sickle cell anemia (SCA), but these are usually small and repetitive, leading ultimately to autosplenectomy. Massive splenic infarcts on the other hand are extremely rare. This is a report of our experience with 8 (4 males and 4 females) cases of massive splenic infarction in patients with SCA. Their ages ranged from 16 to 36 years (mean 22 years). Three presented with left upper quadrant abdominal pain and massive splenic infarction on admission, while the other 5 developed massive splenic infarction while in hospital. In 5 the precipitating factors were high altitude, postoperative, postpartum, salmonella septicemia, and strenuous exercise in one each, while the remaining 3 had severe generalized vasoocclusive crises. Although both ultrasound and CT scan of the abdomen were of diagnostic value, we found CT scan more accurate in delineating the size of infarction. All our patients were managed conservatively with I.V. fluids, analgesia, and blood transfusion when necessary. Diagnostic aspiration under ultrasound guidance was necessary in two patients to differentiate between massive splenic infarction and splenic abscess. Two patients required splenectomy during the same admission because of suspicion of secondary infection and abscess formation, while a third patient had splenectomy 2 months after the attack because of persistent left upper quadrant abdominal pain. In all the 3 histology of the spleen showed congestive splenomegaly with massive infarction. All of our patients survived. Two patients subsequently developed autosplenectomy while the remaining 3 continue to have persistent but asymptomatic splenomegaly. Massive splenic infarction is a rare and unique complication of SCA in the Eastern Province of Saudi Arabia, and for early diagnosis and treatment, physicians caring for these patients should be aware of such a complication.     

Splenic sepsis in sickle cell disease

We describe two patients with sickle cell disease (SCD) who developed infections situated in the spleen. One patient had a splenic abscess and there was strong clinical evidence for an infected splenic infarct in the second patient. SCD predisposes to splenic infection because of functional hyposplenism, defective phagocyte function and splenic infarction. Splenic infections can occur in patients who might be considered to have an absent spleen and the diagnosis of splenic abscess should be considered in individuals with SCD who present with fever and abdominal pain.     

Bacteroides (Parabacteroides) distasonis splenic abscess in a sickle cell patient

Splenic abscess is not an uncommon complication of patients with sickle-cell disease. Here we describe an 18 year-old boy with sickle cell disease and left upper quadrant abdominal pain. Computerized axial tomography revealed left sided free flowing pleural effusion and splenomegaly with liquefaction and possible gas formation. The splenic fluid grew an unusual organism known as Bacteroides distasonis. The patient received antimicrobial therapy and underwent a splenectomy with full recovery. The spleen was cystically infarcted and measured 22 x 16 x 5 cm. The capsule was thickened and covered by fibrinous exudate. Histopathologic examination of the spleen showed complete necrosis with reparative fibrosis. This case presents an unusual cause of splenic abscess due to Bacteroides distasonis with a subacute to chronic course. The presence of fever and left sided pleuritic chest pain in patients with sickle cell disease should raise the suspicion of splenic abscess.     

Case report: splenic infarction and acute splenic sequestration in adults with hemoglobin SC disease.

While acute splenic sequestration and splenic infarction are commonly observed in infants and young children with sickle cell anemia, they are rarely experienced by adult hemoglobin S homozygotes because the recurrent splenic infarction that takes place during childhood is typically followed by scarring, atrophy, and splenic fibrosis. Both acute splenic sequestration and splenic infarction do remain relatively common in adults with the other sickle hemoglobinopathies. These episodes are almost certainly a consequence of the persistently enlarged and distensible spleens that often remain present in these conditions. In this report, the authors describe two adult patients with hemoglobin SC disease: one who developed acute splenic sequestration and one with splenic infarction. In neither case was there a history of recent air travel or exposure to altitude. The clinical course of these two syndromes is presented, and the hematologic, radiologic, and pathologic manifestations are discussed. Because they can sometimes be difficult to distinguish from one another, and because a failure to identify acute splenic sequestration can be catastrophic, these two entities must be included in the differential diagnosis for any hemoglobin SC patient who present with an unexplained fall in hemoglobin, left upper quadrant pain, unexplained fever, or symptomatic splenomegaly.     

Splenic Infarction after Epstein-Barr Virus Infection in a Patient with Hereditary Spherocytosis

We describe the first patient with hereditary spherocytosis (HS) known to have developed splenic infarction following infectious mononucleosis (IM). An 18-year-old Japanese man was referred to our hospital in November 2004 because of continuous fever and icterus. He had undergone cholecystectomy at the age of 14 years. On patient admission in November 2004, a physical examination showed marked hepatosplenomegaly, icterus, and jaundice. He had a white blood cell count of 14.9 x 10(9)/L with 9.5% atypical lymphocytes, a red blood cell count of 2.93 x 10(12)/L, and a hemoglobin concentration of 7.8 g/dL. Microspherocytes were observed in the patient's peripheral blood smear, and immunoglobulin M antibody to Epstein-Barr virus (EBV) viral capsid antigen was detected. The patient's diagnosis was HS with IM. On day 4 of admission, the patient complained of severe abdominal pain. Abdominal computed tomography scanning revealed findings of splenic infarction. Two months after the occurrence of splenic infarction, a splenectomy was performed. A pathohistologic examination of the resected spleen revealed no evidence of thrombosis or arterial occlusion. We assume that the cause of splenic infarction was insufficient blood flow to oxygenate the entire spleen during the acute enlargement of the spleen.     

Sickle cell trait in a white Jewish family presenting as splenic infarction at high altitude

We report the presence of sickle cell trait in several members of a white Jewish family. The trait was discovered when the propositus developed massive splenic infarction at high altitude. No erythrocyte markers characteristic of African ancestry were detected in any of the family members. This is the first bona fide documentation of sickle trait among white Jews.     

Splenic function in persons with sickle cell trait at moderately high altitude

We investigated the possibility that persons with sickle cell trait who reside chronically at moderately high altitude might develop impaired splenic reticuloendothelial function. Seventeen healthy young black men with sickle trait who had lived at greater than or equal to 1,609 m for greater than or equal to 10 years participated in the study along with 25 matched control subjects with normal hemoglobin. Splenic function was assessed by radionuclide liver-spleen scanning and by red cell pit counts. No evidence of impaired splenic function was found in the sickle trait group. The data suggest that long-term residence at moderately high altitude does not place persons with sickle cell trait at risk for splenic dysfunction.     

Reduced levels of T-cell subsets CD4+ and CD8+ in homozygous sickle cell anaemia patients with splenic defects

T-lymphocyte subsets were studied in two patient groups: (1) 50 patients with homozygous sickle cell anaemia (SCA) (mean age 12 (range 3-32) years old) in good health at the time of the study who showed no infectious complication. (2) 50 patients (mean age 13 (range 4-29) years old) with normal haemoglobin rate. The global response revealed a significant increase in levels of CD3+ (P=0.04) and CD8+ (P=0.04) cells when compared with the control group, there was no significant difference in levels of CD4+ cells (P=0.05) between the two groups. However, there was a relationship between T-cell subpopulation levels and spleen status. The average values of T-cell subsets (CD4+ and CD8+) in patients with SCA-induced splenic defects (asplenic, splenomegaly or splenectomized patients) were significantly reduced when compared to SCA patients with normal spleens and the control groups. These data show that T-cell activity was reduced in patients with splenic defects. A correlation between splenic status and a perturbed host defence system in patients with SCA suggests that monitoring T-cell subsets might have prognostic value in the course of sickle cell disease.     

Pulmonary infarction in sickle cell trait.

A young black man presented with unexplained pleuritic chest pain. A hematologic evaluation revealed sickle cell trait, Chest roentgenograms, ventilation/perfusion lung scanning and a pleural-parenchymal lung biopsy documented pulmonary infarction. Sickle cell trait with resultant pulmonary infarction should be considered in black subjects with unexplained pulmonary diseases.     

Splenic sequestration associated with sickle cell trait and hereditary spherocytosis.

Coexistence of sickle cell trait and hereditary spherocytosis (HS) is unusual, and only 16 cases have been reported in the literature. These patients have the same clinical and hematological features as individuals having HS alone. We report a serious complication, acute splenic sequestration crisis (ASSC), occurring in two patients with sickle cell trait and HS. One patient experienced four episodes of ASSC during an 11-year span, while the other had two episodes of this complication during a 4-year period. Red blood cell studies and membrane protein analysis confirmed the diagnosis of HS as a consequence of spectrin deficiency. Splenectomy resulted in marked clinical and hematological improvement in both patients. Histological examination of spleens following splenectomy confirmed that significant erythrostasis and sickling had indeed occurred. ASSC can occur in patients with coexistence of sickle cell trait and HS, and this potentially life-threatening complication should be considered in this condition.     

An extreme consequence of splenectomy in dehydrated hereditary stomatocytosis: gradual thrombo-embolic pulmonary hypertension and lung-heart transplantation

Dehydrated hereditary stomatocytosis (DHS) belongs to the heterogeneous class of hemolytic anemias with leaky red cell membranes. Splenectomy is a highly deleterious treatment, because it favors, with virtually no exception, the occurrence of thromboembolic disease. We describe here the extreme case of a patient with DHS and an associated sickle cell trait. Splenectomy was carried out due to a splenic infarction that occurred during an airplane journey. About 12 years later, the patient noticed an exertional dyspnea, which gradually worsened to such a degree that she became severely incapacitated within 5 years. Eventually, the patient developed a cor pulmonale associated with chronic thromboembolic pulmonary hypertension (CTEPH) and successfully underwent a heart-lung transplant operation. This case ranks as one of the most severe examples ever recorded of the effect that splenectomy may have in DHS patients. Nonetheless, it represents the first case to receive a heart-lung transplant.     

Complications Associated with Sickle Cell Trait: A Brief Narrative Review

Sickle cell trait occurs in approximately 300 million people worldwide, with the highest prevalence of approximately 30% to 40% in sub-Saharan Africa. Long considered a benign carrier state with relative protection against severe malaria, sickle cell trait occasionally can be associated with significant morbidity and mortality. Sickle cell trait is exclusively associated with rare but often fatal renal medullary cancer. Current cumulative evidence is convincing for associations with hematuria, renal papillary necrosis, hyposthenuria, splenic infarction, exertional rhabdomyolysis, and exercise-related sudden death. Sickle cell trait is probably associated with complicated hyphema, venous thromboembolic events, fetal loss, neonatal deaths, and preeclampsia, and possibly associated with acute chest syndrome, asymptomatic bacteriuria, and anemia in pregnancy. There is insufficient evidence to suggest an independent association with retinopathy, cholelithiasis, priapism, leg ulcers, liver necrosis, avascular necrosis of the femoral head, and stroke. Despite these associations, the average life span of individuals with sickle cell trait is similar to that of the general population. Nonetheless, given the large number of people with sickle cell trait, it is important that physicians be aware of these associations.     

An Extreme Consequence of Splenectomy in Dehydrated Hereditary Stomatocytosis: Gradual Thrombo‐embolic Pulmonary Hypertension and Lung–Heart Transplantation

Dehydrated hereditary stomatocytosis (DHS) belongs to the heterogeneous class of hemolytic anemias with leaky red cell membranes. Splenectomy is a highly deleterious treatment, because it favors, with virtually no exception, the occurrence of thrombo‐embolic disease. We describe here the extreme case of a patient with DHS and an associated sickle cell trait. Splenectomy was carried out due to a splenic infarction that occurred during an airplane journey. About 12 years later, the patient noticed an exertional dyspnea, which gradually worsened to such a degree that she became severely incapacitated within 5 years. Eventually, the patient developed a cor pulmonale associated with chronic thrombo‐embolic pulmonary hypertension (CTEPH) and successfully underwent a heart–lung transplant operation. This case ranks as one of the most severe examples ever recorded of the effect that splenectomy may have in DHS patients. Nonetheless, it represents the first case to receive a heart–lung transplant.     

Cerebral Infarction in Children with Sickle Cell Disease: A Concise Overview

Cerebral infarction is a common complication in sickle cell disease. Both overt and silent infarcts evident on neuroimaging have been described. In this article we overview the current knowledge of cerebral infarction in this patient population and discuss recent updates on the role of preventive intervention.     

Cerebral infarction in children with sickle cell disease: a concise overview

Cerebral infarction is a common complication in sickle cell disease. Both overt and silent infarcts evident on neuroimaging have been described. In this article we overview the current knowledge of cerebral infarction in this patient population and discuss recent updates on the role of preventive intervention.     

Sickel cell anemia, the nephrotic syndrome and hypoplastic crisis in a sibship

A family is presented with five siblings, three with sickle cell anemia and two with thalassemia trait. In all three children with sickle cell anemia hypoplastic crises developed after a viral infection. Two of these children were found to have the nephrotic syndrome, as did one of their siblings with thalassemia trait.Renal biopsy in the female patient with sickle cell anemia and the nephrotic syndrome revealed focal and segmental glomerulosclerosis. The biopsies of the other two patients (one with sickle cell anemia and one with thalassemia trait) revealed minimal changes. Hemosiderosis was present only in the biopsy specimens of the two patients with sickle cell anemia. All three patients were steroidresistant. Neither the other two siblings (one with sickle cell anemia and hypoplastic crisis) nor the parents have the nephrotic syndrome.The pathogenesis of nephrotic syndrome in patients with sickle cell anemia is discussed in detail. The current hypotheses relating renal disease to the sickling process are considered. The nephrotic syndrome observed in our patients appears to be familial and unrelated to sickle cell anemia, having been found in family members without, as well as with, sickle cell anemia. The findings in this family suggest that the nephrotic syndrome found in sickle cell anemia may not be causally related, but may be fortuitous, at least in some patients.