Year : 2017 | Volume
: 4 | Issue : 2 | Page : 52--55
Transfusion-dependent anemia in a patient with sickle cell disease as well as HIV-associated tuberculosis
Awwalu Sani1, Bello A Kumo2, Pindiga M Kasim1, Muktar M Haruna1,
1 Department of Haematology, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria
2 Department of Medicine, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria
Department of Haematology, Ahmadu Bello University Teaching Hospital, Zaria
Patients with hemoglobin SC (HbSC) often have unique presentations. Challenges in managing them are further compounded by the presence of other co-morbidities. Transfusion dependence is not a common feature in the course of HbSC. Therefore, when a patient with HbSC becomes transfusion-dependent, then there is a need to evaluate for possible co-morbid conditions. The coexistence of human immunodeficiency virus (HIV) infection and tuberculosis in patients with HbSC is not a common finding, and this poses unique challenges to the managing teams. We present the case of a patient with HbSC with transfusion-dependent anemia, HIV, and disseminated tuberculosis. The challenges faced in the management of this case highlight the importance of a multidisciplinary approach as well as the impact of financial constraints in our setting.
|How to cite this article:|
Sani A, Kumo BA, Kasim PM, Haruna MM. Transfusion-dependent anemia in a patient with sickle cell disease as well as HIV-associated tuberculosis.Sub-Saharan Afr J Med 2017;4:52-55
|How to cite this URL:|
Sani A, Kumo BA, Kasim PM, Haruna MM. Transfusion-dependent anemia in a patient with sickle cell disease as well as HIV-associated tuberculosis. Sub-Saharan Afr J Med [serial online] 2017 [cited 2022 May 26 ];4:52-55
Available from: https://www.ssajm.org/text.asp?2017/4/2/52/228963
Double heterozygous sickle cell disease (SCD) conditions such as hemoglobin SC (HbSC) have a 0.22–1.1% frequency in Nigeria., This condition is often characterized by thromboembolic phenomena, mesenteric infarction, retinitis proliferans, and nephropathy., Hemoglobinopathies additionally are immunosuppressive conditions, and patients usually require aggressive management for infections. Blood transfusions are cardinal features of the holistic management of these conditions.
The frequency of transfusion-dependent anemia among patients with HbSC with concomitant human immunodeficiency virus (HIV) infection and disseminated tuberculosis (DTB) in our environment is largely unknown. Although HbSC is a chronic hemolytic condition, patients are not usually transfusion dependent. The presence of other equally challenging co-morbid conditions poses additional challenges to the managing physicians.
Pulmonary tuberculosis (PTB) and extrapulmonary TB have been reported to be 82 per 100,000 and 246 per 100,000, respectively, among a French cohort of patients with SCD. However, the authors did not find any other cause of compromised immunity among this cohort other than functional asplenia. Nouraie et al. reported an overall lower frequency of HIV infection among patients with SCD compared to Hemoglobin AA (HbAA) controls; 1.5% versus 3.3%.
While some factors have been suggested to inhibit the progression of HIV among patients with SCD, other factors may promote HIV progression in this group of patients. Bagasra et al. have suggested that inhibition of HIV progression may be due to the autosplenectomy among patients with SCD leading to loss of an important site where HIV replicates. Ongoing upregulation of inflammation, hemolysis, and iron overload may be additional contributory factors. Poor complement activation and defective cell-mediated immune responses among patients with SCD, however, may promote progression. Interestingly, Cheis and Hutz have described a comparatively higher frequency of the CCR5Δ32 allele among patients with SCD compared to HbAA controls in Brazil. This mutant is known to confer resistance to HIV.
The mechanism of anemia in HIV infection is multifactorial. These include nutritional deficiencies, autoimmune states, parasitic infestations, direct suppression of bone marrow progenitors, renal causes with reduced erythropoietin secretion and adverse effects of drugs. Both HIV infection and PTB have been implicated in anemia of chronic diseases.
We present a case of a patient with HbSC with transfusion-dependent anemia with co-morbid DTB, HIV infection, alcoholic chronic liver disease (CLD) with possible malignant transformation.
A 43-year-old patient with SCD (HbSC) presented to our center with a history of having received three units of blood in the preceding 3 weeks. Despite these transfusions, he still had features of chronic severe anemia, cough, and generalized body swellings, more in the lower limbs. He had been diagnosed with PTB 3 months before in another center and commenced on anti-TB drugs. He was also diagnosed HIV positive from the referring hospital; on account of which, he was commenced on Highly Active Antiretroviral Therapy (HAART) (abacavir, lamivudine, lopinavir, and ritonavir) 1 month prior to presentation. He had ingested significant quantities of alcohol over the past 10 years.
He was chronically ill-looking, middle-aged man, febrile, severely pale, deeply jaundiced with grade IV finger clubbing, peripheral lymphadenopathy and pitting pedal edema. He was dyspneic with dull percussion notes over the upper lung zones bilaterally with basal crepitations. Cardiovascular examination revealed pulse rate of 94 beats per minute, along with a blood pressure of 90/60 mmHg with 1st, 2nd, and 3rd heart sounds. His abdomen was distended with a hard, tender hepatomegaly.
Laboratory assessment revealed severe anemia with Packed Cell Volume (PCV) of 15% and reticulocyte of 1% with a reticulocyte index of 0.1. He raised red cell indices; mean corpuscular volume 108 fL, mean corpuscular hemoglobin 42.8 pg and mean corpuscular hemoglobin concentration 39.6 g/dL. There were normal leukocytes and platelets counts, and elevated Erythrocyte Sedimentation Rate (ESR). Chest X-ray revealed features consistent with PTB. Serum urea, sodium, potassium, chloride, bicarbonate, and creatinine levels were 3.2 mmol/L, 144 mmol/L, 4.4 mmol/L, 105 mmol/L, 23 mmol/L, and 95 μmol/L, respectively. His viral load was 4797 copies/mL, and CD4 count was 252 cells/μL.
Liver function tests revealed elevated alkaline phosphatase of 841 IU/L, total bilirubin of 163 IU/L, and conjugated bilirubin of 113 IU/L. Viral screening results for Hepatitis B Surface Antigen (HBsAg) and Hepatitis C Virus (HCV) were negative. Ultrasonography revealed an enlarged liver with mildly coarsened echotexture, and increased parenchymal echogenicity in addition to multiple ill-defined masses. Bone Marrow examination revealed hypercellular fragments and cell trails with myeloid erythroid reversal. Erythropoeisis showed predominant megaloblastic maturation with few micronormoblasts. There were giant myelocytes, metamyelocytes, and band forms. Megakaryopoeisis was present with numerous dysplastic forms. Bone marrow stain for acid-fast bacilli was negative. No foreign cells were seen in the bone marrow. GeneXpert test could not be conducted.
A diagnosis of anemic heart failure in a patient with HbSC with HIV-associated dyshemopoiesis and DTB was made. He was managed with subcutaneous erythropoietin, intramuscular vitamin B12, and oral folic acid. Additional working diagnoses were those of drug-induced hepatitis, CLD with likely malignant transformation and alcoholic liver disease. He was further placed on intravenous (iv) furosemide, oral spironolactone, and iv ceftriaxone because he was found to be febrile upon review and sepsis. He received a total of three units of HbAA red blood cells during this period. Although he was able to procure erythropoietin, he could not procure G-CSF due to financial constraints.
During the course of admission patient’s PCV appreciated to 30%, all symptoms resolved, and he was subsequently discharged after 30 days on admission. During the follow-up period, over 55 days, the PCV dropped again to 21.1%. The follow-up period was also characterized by financial constraints limiting compliance with erythropoietin and regular follow-up visits.
Subsequently, the patient was readmitted 74 days after discharge, on the account of high-grade fever, cough, and diarrhea. He was pale and febrile. He had severe anemia (PCV − 14.7%), leukopenia (white blood cells (WBC) count − 0.4 × 109/L), and thrombocytopenia (platelet count − 80 × 109/L). He was subsequently transfused with ABO compatible blood, and he received antibiotics among other drugs. Erythropoietin and Granulocyte-Colony Stimulating Factor (G-CSF) were not procured throughout the period of re-admission. Three days into the re-admission, he developed confusion and irrational talk with features of meningeal irritation. His Glascow Coma Score dropped to 9/15. Despite intensive multidisciplinary management involving neurologists, hematologists, gastroenterologists, and respiratory physicians, his condition rapidly deteriorated, and he died 4 h later. Request for post-mortem examination was declined by his relatives.
Presence of anemia in SCD is not uncommon, and anemia has been documented to complicate chronic illnesses such as TB and HIV/AIDS. This patient presented with severe anemia despite receiving three units of blood over 3 weeks. Although the patient’s steady state PCV was not known, it can still be deduced that he had become transfusion-dependent as Nigerian patients with HbSC have been shown to have mild to moderate anemia with PCV ranging from 27.3 to 33.04%.,
This patient presented in the continuation phase of a rifampicin-based anti-TB therapy without a documentation of how the TB was diagnosed or why he was on a Protease Inhibitor (PI) based HAART regimen. Additionally, there was no documentation of parameters such as viral load and CD4 counts. This highlights the need to improve documentations especially upon referral.
The raised alkaline phosphatise in this patient may be consistent with SCD because it has been shown to be raised both in crises and during asymptomatic periods. The presence of conjugated hyperbilirubinaemia, an uncommon finding in SCDs, may be due to intrahepatic causes because ultrasonographic findings were those of coarsened, increased parenchymal echogenicity and multiple ill-defined masses. Unfortunately liver biopsy could not be performed up to the demise of this patient.
His transfusion dependence may be attributed to the effect of co-infection with HIV and TB. Cytokine dysregulation and direct infection of progenitors of red blood cells may have been responsible for the worsening anemia in this patient., The presence of megaloblasts and dysplastic megakaryocytes in this patient reflects a dyserythropoietic process consistent with chronic illnesses such as HIV and TB. Anemia of chronic diseases is also a feature of HIV and PTB. Therefore, transfusion therapy alone would not have been adequate.
Erythropoietin has been shown to produce positive results in HIV associated dyshemopoiesis. The use of hematinics and an erythropoiesis-stimulating agent, erythropoietin, was able to reduce transfusion demand in this patient. This is because prior to admission, he received an average of one unit of blood every week; however, he remained transfusion-free for 55 days while on follow-up. His PCV further reduced to 14.7% upon readmission. Unfortunately, due to financial constraints, he could not sustain the erythropoietin therapy. The pancytopenia upon readmission suggests a worsening of the patient’s hemotologic stability and also prognosis. The foregoing coupled with the features suggestive of meningitis may explain why the period of readmission was brief and fatal.
Although the ingestion of >50 g of alcohol/day for 10 years is considered a risk factor for alcoholic liver disease, this condition may arise with lesser amounts. Other factors may modulate this. These include genetic predisposition, poor nutrition, and concomitant viral hepatitis.
CLD due to alcohol and hepatitis C infection are frequently associated with hematologic abnormalities. The etiology of anemia is diverse in over 75% of CLD patients. Of the various etiologic factors of anemia in CLD, the most important in this patient is that alcohol has direct toxic effects on erythrocyte precursors in the bone marrow.
Cirrhotic patients frequently develop deficiencies of folic acid and vitamin B12 as a result of decreased food intake and malabsorption of nutrients. In addition, alcohol also has weak antifolate activity. Bone marrow megaloblastic erythropoiesis has been described in cirrhotics with folate and vitamin B12 deficiency., These are evident in the index patient. Additionally, the anti-TB drugs might have contributed to the anemia in this patient because it has been shown that these drugs are associated with a significant fall in hematocrit levels.The initial presentation of this patient is highly suggestive of a paradoxical TB-associated immune reconstitution inflammatory syndrome (IRIS). He, however, responded very well to the managements instituted and remained on follow-up for 74 days before readmission. Although paradoxical TB-associated IRIS may be self-limiting, it may be fulminant and life threatening. Fever, pulmonary infiltrates, adenopathies, decreasing viral load, and increasing CD4 count are some features of IRIS., However, transfusion dependence and marked bone marrow dyshemopoiesis are not documented presentations.
There were numerous delays and constraints in this patient’s management. Blood transfusion could not be administered when required. This may be attributed to the reliance on directed, replacement donors as voluntary nonremunerated blood donation is still poor in our setting. Additionally the growth factors were not affordable. Fortunately drugs for TB and HIV were available as they are free.
This case has shown that the presence of SCD and co-infections with HIV and TB, in the same patient, each of which is independently capable of causing anemia can pose a management challenge in our setting. Additionally, the utility of a multidisciplinary approach in management is evident. We recommend that transfusion dependence in SCD patients should be fully evaluated and advocacy on the need for post-mortem be strengthened.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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