|Year : 2018 | Volume
| Issue : 3 | Page : 157-161
Basic hemostatic parameters in adults with sickle cell anemia at Ahmadu Bello University Teaching Hospital, Zaria Nigeria
Ibrahim Usman Kusfa, Sirajo Mohammed Aminu, Aisha Indo Mamman, Abdulaziz Hassan, Aliyu Ahmadu Babadoko, Muktar Haruna Mohammed, Ismaila Nda Ibrahim, Yahaya Garba
Department of Haematology and Blood Transfusion, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria
|Date of Web Publication||4-Oct-2018|
Dr. Ibrahim Usman Kusfa
Department of Haematology, Ahmadu Bello University Teaching Hospital, Zaria
Background: Reports from various studies showed that patients with sickle cell anemia (SCA) have altered components of hemostasis such as platelet function, the procoagulant, anticoagulant, and the fibrinolytic pathways. These altered components may be different or the same based on regions, racial, or environment. Determining the basic hemostatic parameters in our environment is imperative because from records this may be the first time such a study is being carried out and the altered components so involved may give an insight as to the clinical phenotypes we have in our setting. The data obtained from this study may also provide reference values appropriate for therapeutic intervention. The objective of this study is to determine some basic hemostatic parameters in patients with SCA in steady state attending the hematology clinic of Ahmadu Bello University Teaching Hospital Zaria, Nigeria. Materials and Methods: We conducted a case–control study involving fifty patients with SCA (HbSS) in steady state and 25 healthy volunteers with normal hemoglobin (HbAA) as controls between the ages of 15 and 50 years, with females comprising 40 (53.0%) and 35 (47.0%) males. Steady state refers to a point in time where a patient with SCA is not experiencing an acute painful crisis or any changes due to therapy for at least four consecutive weeks after a previous painful crisis. Platelet count was determined by hematology analyzer (Sysmex XT–2000i, Sysmex Corporation, CPO Box1002 Kobe 650–8691, Japan) while bleeding time (BT) was performed using Ivy's method, using disposable Bevel lancet with the test carried out in duplicate and superficial veins were avoided. Prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT) were estimated using semi-automated coagulation analyzer. Results: The age ranges of both the patients and the controls were 15–50 years and 15–34 years with mean ages of both was 23.80 ± 7.46 and 24.28 ± 3.48 years (P = 0.76) respectively. Females comprised 53.0% of all the study participants. The mean values of hemostatic parameters in the SCA and controls groups were: Platelets (499.82 ± 208.23 vs. 230.36 ± 106.65 × 109/L, 95% confidence interval [CI]; 180.9881, 357.9319, P < 0.0001), BT (2.99 ± 0.98 vs. 2.94 ± 0.92 min, −0.4219, 0.5139, P = 0.845), PT (12.43 ± 3.11 vs. 13.18 ± 1.11 s, 95% CI; −2.0335, 0.5335, P 0.248), ±8.80 vs. 17.20 ± 5.11 s, 95% CI; 0.4874, 8.0846, P = 0.028), respectively. Conclusion: A significant increase in platelet count, TT and a significant decrease in APTT were observed in patients with SCA. These can be an evidence of hypercoagulable nature of SCA. We recommend that patients with SCA, especially those with frequent and severe vaso-occlusive crises should have these basic hemostatic tests as a baseline and during routine clinic follow-up for improved patient management.
Keywords: Hemostasis, sickle cell anemia, steady state, volunteers
|How to cite this article:|
Kusfa IU, Aminu SM, Mamman AI, Hassan A, Babadoko AA, Mohammed MH, Ibrahim IN, Garba Y. Basic hemostatic parameters in adults with sickle cell anemia at Ahmadu Bello University Teaching Hospital, Zaria Nigeria. Sahel Med J 2018;21:157-61
|How to cite this URL:|
Kusfa IU, Aminu SM, Mamman AI, Hassan A, Babadoko AA, Mohammed MH, Ibrahim IN, Garba Y. Basic hemostatic parameters in adults with sickle cell anemia at Ahmadu Bello University Teaching Hospital, Zaria Nigeria. Sahel Med J [serial online] 2018 [cited 2019 May 24];21:157-61. Available from: http://www.smjonline.org/text.asp?2018/21/3/157/242741
| Introduction|| |
Sickle cell disease is a term used for a group of hemoglobinopathies in which the presence of the sickle cell gene gives rise to clinical features in association with other abnormal hemoglobin. However, if the sickle cell gene is present in homozygous state, it is called sickle cell anemia (SCA). The SCA is in most cases the severest form of sickle cell diseases.
SCA is an inherited condition resulting from the inheritance of two sickle genes. SCA is one of the most common genetic disorders worldwide based on the World Health Organization published global prevalence of SCD and other data, an estimated 20–25 million individuals are homozygous (HbSS) worldwide. About 12–15 million in sub-Saharan Africa, the highest gene frequency is in tropical Africa. Nigeria bears the highest burden of SCA in the world with about 3% of the population being homozygous.
Nearly, every component of hemostasis namely platelet function, the procoagulant, the anticoagulant as well as the fibrinolytic systems in favor of a procoagulant phenotype in the disease, SCA is frequently referred to as a “hypercoagulable state.” Abnormal exposure of phosphatidylserine (PS) in sickle erythrocytes may occur due to repeated cycles of sickling and unsickling linked to polymerization and depolymerization of HbSS that results in the production of terminal spicules or microvesicles with exposed PS. Again, external exposure of PS alters the adhesive properties of sickle red blood cell (RBC) and appears to be involved in the hemostatic changes observed in SCA.,, It has also been observed that plasma levels of prothrombin fragments 1.2 (F 1.2) are associated with the number of circulating PS-positive RBC.
Patients with SCA have increased levels of markers of thrombin generation and thrombin-antithrombin complexes (F 1.2, TAT complexes) in the noncrisis state., There is an abundance of evidence suggesting that circulating platelets in patients with SCA are chronically activated. This activation may contribute to the observed hypercoagulability state in SCA. Platelets aggregation responses do appear to be increased in adults patients with SCA in the noncrisis steady state. This may be due to circulating levels of young metabolically active platelets, or increased plasma levels of platelets agonists such as thrombin, adenosine diphosphate, and epinephrine.
In addition to elevated plasma levels of α-granule constituents, thrombospondin, platelet factor 4, and β-thromboglobulin, platelet-derived plasma sCD40 L (soluble CD40 ligand) is also elevated in the noncrisis steady state, compared to control patients. Hemolysis, with decreased bioavailability of nitric oxide, may contribute to the pathogenesis of platelets activation in SCA.
Knowing the steady state values is extremely important in evaluating patients who present themselves with acute vaso-occlusive crises. Therefore, comparing data during the acute vaso-occlusive crisis with the steady state values often reveals objective changes during crisis. Therefore, prolonged survival of patients with SCA is associated with increased risk for thrombosis. Hemostatic parameters obtained from participants of this study will provide reference values appropriate for therapeutic intervention if the need arises.
| Methods|| |
It was a case–control study involving 75 participants, and comprised 50 patients with SCA (HbSS) in steady state and 25 healthy volunteers (HbAA) as controls between the ages of 15 and 50 years, with females comprising 40 (53.0%) and 35 (47.0%) males at the hematology clinic. The inclusion criteria for this study are adult participants with HbSS only in a steady state while those with hypercoagulable comorbid states (hypertension, diabetes mellitus, pregnancy), patients on contraceptives, aspirin and those with known bleeding disorders or thromboembolism were excluded from the study. Ethical approval was obtained from the Health Research Ethic Committee of the Ahmadu Bello University Teaching Hospital, Zaria. Informed, written consent was obtained from all the participants in the study after due explanation of the nature of the study and the data obtained in this study will be treated with strict confidentiality. Venous blood of 7.5 ml (7.5 ml) was drawn from the cubital vein, 3 ml of which was dispensed into the ethylenediamine tetraacetic acid-containing bottle (EDTA) for full blood count using automated hematology analyzer (SYSMEX XT-2000i, SYSMEX CORPORATION, CPO BOX 1002 KOBE 650–8691, Japan) while the remaining 4.5 mls of the blood was dispensed into a bottle containing 0.5 mls of 3.2% trisodium citrate for the determination of partial thromboplastin time prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT) using semi-automated hematology analyzer (Diagnostica Stago ST art® 4, coagulation analyzer, France) with strict adherence to the manufacturer's instructions, while bleeding time (BT) was done using Ivy's method, using disposable Bevel lancet with the test carried out in duplicate and superficial veins were avoided. Frequencies, proportions, and student t-test were performed to compare the means of hemostatic parameters in steady SCA subject with the controls using International Business Machines Corporation (IBM) SPSS version 20.0. The level of significance was set at ≤0.05.
| Results|| |
The mean age of both the patients and the controls was 23.80 ± 7.46 and 24.28 ± 3.48 years respectively, comprising of 40 (53.0%) females. The mean values of hemostatic parameters in the SCA and controls groups were: Platelets (499.82 ± 208.23 vs. 230.36 ± 106.65 × 109/L, 95% confidence interval [CI]; 180.9881, 357.9319, P < 0.0001), BT (2.99 ± 0.98 vs. 2.94 ± 0.92 min, 95% CI; 0.4219, 0.5139, P = 0.845), PT (12.43 ± 3.11 vs. 13.18 ± 1.11 s, 95% CI; −2.0335, 0.5335, P = 0.248), APTT (30.32 ± 4.50 vs. 33.76 ± 3.67 s, 95% CI; −5.5168, −1.3752, P = < 0.0001), and TT (21.48 ± 8.80 vs. 17.20 ± 5.11 s, 95% CI; 0.4874, 8.0846, P = 0.028).
| Discussion|| |
The mean PT of patients with SCA in this study was shorter than that of the controls, but there was no statistically significant difference [Table 1]. This is contrary to the findings by Leslie et al. and Wright et al. who reported a prolong PT values among the SCA patients than the controls even though the mean values of both were within normal limits. Prolonged PT by Leslie et al. and Wright et al. may be due to chronic consumption of coagulation factors from enhanced procoagulant activity. Moreover, liver dysfunction resulting from anoxia secondary to sinusoidal obstruction by sickling RBCs, iron overload and repeated thrombosis with necrosis of liver parenchyma can result in decrease synthesis of these factors. However, the shorter values in this study may be attributed to the activated coagulation factors and also by products of intravascular hemolysis., Again it might be due to ongoing subclinical vaso-occlusion with attendant thrombosis at microvascular level leading to microthrombosis and subsequent fibrin deposition which triggers a vicious cycle of coagulation manifesting as shortened PT.
|Table 1: Comparison of means of basic hemostatic parameters of all the study participants|
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The mean APTT of patients with SCA was shorter compared to the control [Table 1]. This is similar to the earlier studies by Leslie et al. who expressed shorter values among the SCA patients than the controls. These shorter values might explain the hypercoagulable nature of SCD., It is also pertinent to note that patients with SCA suffer from the continuous cycle of micro-vasoocclusion and this leads to subclinical ischemic episodes even in steady state with a subsequent decrease in APTT.
The mean TT of the patients with SCA was relatively longer than that of the controls [Table 1]. This is comparable to those reported by Westerman et al. and Tomer et al. in separate studies. This may be explained by the marked activation of markers of thrombin generation in patients with SCA. Similar results were also reported by Wood et al. and Devaux and Zachowsky in patients with SCA in steady state. However, Nikolas et al. reported a shorter TT among patients with SCA, though difficult to explain.
The mean platelets count was higher among patients with SCA than the controls [Table 1]. This is supported by the previous reports of Aliyu et al., and other studies by Liesner et al., Walters et al.,,and Green et al., Higher platelets count in patients with SCA may explain the cellular activation previously observed in SCA individuals., Higher platelets count in these patients may also be due to functional asplenia and chronic hemolysis. It may also be due to functional asplenia, increased erythropoietic activity as well as thrombopoietin activity resulting in chronic anemia. This may contribute to thrombosis in patients with SCA.
The mean BT of both groups was the same [Table 1]. This may suggest preservation of platelets function and normal vascular integrity despite high count. However, Ataga and Orringer found out a shortened BT in patients with SCA which he termed as a curious paradox and traced it to nature's ways of arresting bleeding in SCA patients.
| Conclusion|| |
A significant increase in platelet count, TT and decrease in APTT was observed in patients with SCA. Therefore, data obtained from this study will provide reference values appropriate for therapeutic interventions in patients with SCA as they now have prolonged life span which may predispose them to SCA-related thrombotic complications.
We recommend that patients with SCA, especially those with frequent and severe vaso-occlusive crises should have these basic hemostatic tests as a baseline and during routine clinic follow-up for improved management.
Future study in patients with SCA should include C-reactive protein to rule out any form of vaso-occlusive crises. Platelet function analyzer-100 should be employed in the future studies which are more sensitive than BT. Liver function tests should have been evaluated in these patients to know the extent of liver involvement. Patients in this study were recruited from a specialty clinic at a tertiary care medical center, and may not represent all patients with SCA.
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Conflicts of interest
There are no conflicts of interest.
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