Recurrent chronic leg ulcers and its are morbidities associated with sickle cell anaemia (SCA). Compression therapy increases the rate of healing of these ulcers and also decreases the rate of recurrence.
This study evaluated the haematological parameters of patients with SCA and chronic leg ulcers placed on high compression bandaging to provide data for improved ulcer management and prevention.
Eighteen patients with SCA and chronic leg ulcers were recruited for treatment by compression therapy in Ibadan, Nigeria, from March to June 2015. Eighteen SCA patients with no history of chronic leg ulcers were age and sex matched and recruited as controls. Blood samples, wound biopsies and swabs were collected at different time points for full blood count, microbiology, culture and antimicrobial susceptibility tests. Haemoglobin variants were quantified by high performance liquid chromatography. Fasting blood sugar was tested for leg ulcer patients to determine diabetic status.
Ulcers ranged from 0.5 cm2 to 416 cm2 (median: 38.4 cm2). Post-intervention ulcer size ranged from 0.0 cm2 to 272 cm2 (median: 18.6 cm2,
Measures to improve haematological parameters during leg ulcer treatment in SCA patients should be taken to aid wound healing.
Chronic leg ulcer is one of the morbidities associated with sickle cell anaemia (SCA). Chronic leg ulcer is a wound on the skin that occurs between the knee and the foot, showing no signs of healing after 3 months of proper treatment.
Sickle cell associated ulcers (SCUs) can be precipitated by many factors such as trauma, infection, severe anaemia and usually occur with venous stasis disease, which requires compression therapy.
Ulcer incidence in sickle cell disease (SCD) patients in the United States ranges from 2.5% to 25% and 75% in Jamaica.
This study was approved by the University of Ibadan/University College Hospital Joint Ethics Review Committee, College of Medicine, University of Ibadan; protocol identification number UI/EC/15/0133. Sickle cell disease patients in need of leg ulcer treatment at the haematological clinics of the University College Hospital and Ring Road State Hospital, Ibadan, voluntarily participated in this study. Oral informed consent was obtained from each of the participants using a format explaining the details of the procedure, possible complications that may arise using the compression therapy technique for wound care and the importance of the biopsies and periodic blood sample collection. A code number was assigned to each patient and their samples to protect participants’ privacy.
In a pilot hospital-based study, 18 SCA patients with chronic leg ulcers were recruited from haematology clinics at University College Hospital and Ring Road State Hospital, Ibadan, for treatment by compression therapy (first use case in Nigeria) for a period of 3 months (13 weeks) between March 2015 and June 2015. There were 6 men and 12 women with ages ranging from 19 to 44 years. Eighteen age and sex matched SCA patients with no history of chronic leg ulcers were recruited as controls. Sickle cell anaemia patients below 18 years as well as adult SCA patients attending the named facilities who did not give informed consent were excluded from this study. Those with chronic leg ulcers with an ankle brachial pressure index less than 0.8 were also excluded. A pre-tested semi-structured questionnaire was administered to each of the patients for a history of leg ulcer, family history and socio-demographic details.
A four-layer high compression bandaging system described previously.
Blood samples were collected before commencement of treatment (T0) from both groups. For the leg ulcer group, blood samples, wound swabs and tissue biopsies (in normal saline and in peptone) were also collected on the 5th week (T1) and 10th week (T2) of treatment. Microscopy, culture and sensitivity tests were carried out on the wound biopsies and swabs. Full blood count was carried out using a Swelab Haematology Analyser (Boule Diagnostics, Stockholm, Sweden) and the level of haemoglobin variants was determined by high performance liquid chromatography using the BioRad Variant II Hemoglobin Testing System (Clinical Diagnostics, Hercules, California, United States). The patients were prescribed antibiotics based on the result of antibiotic sensitivity tests. A fasting blood sugar test was performed for the leg ulcer patients to determine their diabetic status.
Statistical analyses were done using IBM Statistical Package for Social Sciences version 23 (IBM Corporation, Armonk, New York, United States). The differences in haematological parameters between the control and test groups were determined by the student’s
Eighteen patients with leg-ulcers and a similar number of ulcer-free controls were included in the study. There were 25 uclers in all as seven patients had bilateral ulcers. The ulcers ranged from 0.5 cm2 to 416 cm2 with a median ulcer size of 38.4 cm2. The ages of the ulcers were 1–22 years (with recurrence). Within the 3 months of compression therapy, four of the patients had complete close-up of the ulcer wound, 16 of them had more than a 50% healing rate (the percentage of the size of wound closure to the initial wound size) and the remaining five had a healing rate of 35% – 50%. The post-intervention median ulcer size ranged from 0.0 cm2 to 272 cm2 with a median of 18.6 cm2 (
Haematocrit (HCT) at commencement of treatment was lower in the leg ulcer patients compared to the control group (19.11% vs 26.17%,
Mean values for full blood count parameters across the different time periods in adult sickle cell anaemia patients with (cases) and without (controls) chronic leg ulcers at the University College Hospital and Ring Road State Hospital, Ibadan, Nigeria, March–June 2015.
Time period | HGB (g/dL) | RBC (1012/L) | HCT (%) | MCV (fL) | RDW % | MCH (pg) | MCHC (g/dL) | WBC (103/µL) | LYMF (%) | MID % | GRAN (%) | PLT (103/ |
MPV ( |
PCT % | PDW ( |
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T0 | 6.17 ± 1.37 | 2.05 ± 0.67 | 19.11 ± 4.44 | 95.33 ± 10.91 | 27.78 ± 7.54 | 30.82 ± 3.85 | 32.59 ± 1.36 | 13.90 ± 4.9 | 38.03 ± 10.35 | 7.07 ± 2.17 | 54.88 ± 12.01 | 487.42 ± 193.92 | 8.75 ± 0.65 | 0.42 ± 0.17 | 10.99 ± 1.48 |
T1 | 6.54 ± 1.31 | 2.16 ± 0.67 | 19.79 ± 4.35 | 93.85 ± 10.54 | 25.62 ± 3.03 | 31.26 ± 3.96 | 33.26 ± 1.41 | 13.1 ± 2.90 | 39.58 ± 8.89 | 5.21± 1.43 | 55.02 ± 9.30 | 408.71 ± 137.04 | 8.69 ± 0.54 | 0.36 ± 0.11 | 11.32 ± 0.75 |
T2 | 6.62 ± 1.28 | 2.24 ± 0.69 | 20.58 ± 4.29 | 94.99 ± 11.22 | 25.82 ± 3.75 | 30.68 ± 4.11 | 32.22± 0.99 | 11.88 ± 4.14 | 39.36 ± 10.0 | 7.62 ± 1.87 | 50.78 ± 15.37 | 495.62 ± 191.50 | 9.58 ± 1.25 | 0.47 ± 0.17 | 12.16 ± 1.64 |
Control group | 8.43 ± 1.18 | 3.03 ± 0.6 | 26.17 ± 3.98 | 87.73 ± 11. 21 | 22.68 ± 2.73 | 28.46 ± 4.45 | 32.3 ± 1. 49 | 8.70 ± 1.92 | 45.74 ± 12.64 | 8.14 ± 3.8 | 46.97 ± 13.07 | 299.08 ± 109.03 | 8.68 ± 0.93 | 0. 26 ± 0.1 | 11.30 ± 1.21 |
< 0.001 | < 0.001 | < 0.001 | 0.02 | 0.004 | 0.05 | 0.27 | < 0.001 | 0.03 | 0.15 | 0.03 | < 0.001 | 0.42 | < 0.001 | 0.25 |
HGB, haemoglobin concentration; RBC, red blood cell count; HCT, haematocrit; MCV, mean corpuscular volume; RDW, red cell distribution width; MCH, mean corpuscular haemoglobin; MCHC, mean corpuscular haemoglobin concentration; WBC, white blood cell count; LYMF, lymphocyte count; GRAN, granulocyte count; MID, other white blood cells that are not lymphocytes nor granulocytes; PLT, platelet count; MPV, mean platelet volume; PCT, volume of platelets in blood; PDW, platelet distribution width.
T0, Before commencement of treatment; T1, 5th week of treatment; T2, 10th week of treatment.
There was a positive correlation between wound size and WBC (0.538,
Correlation between wound size and some haematological parameters at T0 in adult sickle cell anaemia patients with chronic leg ulcers at the University College Hospital and Ring Road State Hospital, Ibadan, Nigeria, March–June 2015. Correlation between wound size (cm2) and (a) Wound size versus white blood cell count (103/
In the patients with chronic leg ulcers, there was a positive correlation between WBC and PLT and negative correlations between WBC and HGB as well as between HGB and PLT with and without exclusion of the patient with the biggest ulcer at T0. There was no correlation between any of these three parameters in the patients who had not experienced a chronic leg ulcer in their lifetime (i.e. the control group) (
Correlation between white blood cell count, platelet count and haemoglobin concentration at T0 in adult sickle cell anaemia patients with (cases) and without (controls) chronic leg ulcers at the University College Hospital and Ring Road State Hospital, Ibadan, Nigeria, March 2015 – June 2015.
Haematological parameters | Cases ( |
Cases ( |
Controls ( |
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PLT | HGB | PLT | HGB | PLT | HGB | |
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PLT, platelet count; HGB, haemoglobin concentration; WBC, white blood cell count.
The concentration of HbS was higher in the leg ulcer group (86.25% vs 82.87%,
Bacteria isolated from the wound swabs and biopsies include
None of the leg ulcer patients was diabetic. Results of the fasting blood sugar test for all the participants in the test group ranged from 64 mg/dL to 82 mg/dL.
This study was carried out to evaluate the haematological parameters in patients with SCA and chronic leg ulcers, and also to assess the haematological changes during healing of these ulcers while being managed with high compression bandaging, an as yet unemployed method of chronic leg ulcer treatment in Nigeria. There were marked differences in some haematological parameters between SCA patients with and without chronic leg ulcers and haematological parameters improved with healing of the ulcers. Monitoring of haematological parameters for improvement during treatment of chronic leg ulcers and after wound closure in SCA patients will aid healing and might also reduce the rate of recurrence.
The mean HGB and HCT of the case patients (those with chronic leg ulcers) at T0 were significantly lower than those of the control patients (those who have never had a chronic leg ulcer). A high rate of haemolysis is one of the major causes of a reduced steady state haemoglobin in sickle cell patients. Sickle cell anaemia patients with a lower steady state haemoglobin concentration are at a higher risk of developing chronic leg ulcer.
A wider red cell distribution width as compared to the control group, with a mean corpuscular volume within normal haematological range, in the test patients alludes to anaemia caused by bleeding from regular treatments, folate deficiency or vitamin B12 deficiency. There was a slight improvement in the HCT level from T0 to T2 mainly due to constant education of the patients on the need to improve the quality of their diet and better compliance with routine haematinics.
Nolan et al.
There was a significantly higher number of platelets in the leg ulcer patients than in the control group of this study. In Jamaica, Cumming et al.
There was a negative correlation between HGB and WBC as well as between HGB and PLT. This means a higher rate of haemolysis may result in elevated WBC and PLT counts. The observation that these three parameters were not significantly correlated in patients without chronic leg ulcers lends credence to the notion that lower steady state HGB and elevated WBC and PLT counts may predispose sickle cell patients to chronic leg ulcers.
Koshy et al.
The level of HbS was lower in the control patients. A lower HbS level is usually due to higher HbF levels or the presence of alpha or beta thalassemia which was not assayed in this study. Reduced HbS concentration leads to a lower rate of sickling and, consequently, a reduced rate of haemolysis. Haemolysis of sickled RBCs leads to the release of activated molecules (plasma haemoglobin) which react with nitric oxide to form inert nitrate. Nitric oxide maintains vascular function and normal blood flow
None of the chronic leg ulcer patients in this study was diabetic. Diabetes is quite rare in sickle cell patients
Compression therapy aids healing of leg ulcers by increasing venous blood flow,
Chronic leg ulcer is multifactorial and hence, in order to make the correct diagnosis and give the most effective treatment, health practitioners should adopt a multidisciplinary approach to a systematic patient evaluation to determine the ulcer pathogenesis.
One limitation of this study is the small sample size. The high cost of compression therapy was the major determinant of the sample size. Laboratory markers such as elevated serum lactose dehydrogenase, reticulocyte count, bilirubin level and some genetic factors which were not assayed in this study have also been associated with a risk of chronic leg ulcers in patients with SCD,
Sickle cell patients with a lower level of HGB and elevated WBC and PLT counts at steady state may be at a higher risk of non-healing leg ulcers. Most of the haematological indices improved with healing of the leg ulcers placed on high compression bandaging. An interdisciplinary approach to provide a favourable microenvironment for healing of ulcers, and the monitoring of haematological parameters for the prevention of recurrence, is recommended.
Sickle Cell Hope Alive Foundation (SCHAF) – or the recruitment of patients and provision of funds for this study. The members of staff of Haematology Department, Ring Road State Hospital, Ibadan, who cooperated and contributed their time to make this study possible. The patients who cooperated and endured the pain of biopsies and treatment. Medical Education Partnership Initiative in Nigeria (National Institute of Health) – For providing guidance in the data analysis and write-up of this work.
The authors have declared that no competing interests exist.
O.A.B. was involved in the design, planning, investigation and data analysis of the study and the manuscript write-up. A.O. was involved in the design, planning and investigation. A.B.O. and C.P.B. assisted with the planning and implementation of the study. F.F. revised the manuscript. A.A.O. assisted with the microbiology investigation. A.G.F. was involved in the study design and planning, and assisted with secondary level facility access, project coordination and manuscript revision.
Funding was provided by the Sickle Cell Hope Alive Foundation (SCHAF).
Data sharing is not applicable to this article as no new data were created or analysed in this study.
The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of any affiliated agency of the authors.