|Year : 2017 | Volume
| Issue : 3 | Page : 117-122
Red cell distribution width as a predictive index for multiorgan damage in disseminated intravascular coagulation
Sagir G Ahmed1, Modu B Kagu2, Umma A Ibrahim3
1 Department of Haematology, Aminu Kano Teaching Hospital, Kano, Kano State, Nigeria
2 Department of Haematology, University of Maiduguri Teaching Hospital, Maiduguri, Borno State, Nigeria
3 Department of Paediatrics, Aminu Kano Teaching Hospital, Kano, Kano State, Nigeria
|Date of Submission||01-Sep-2017|
|Date of Acceptance||01-Oct-2017|
|Date of Web Publication||9-Nov-2017|
Sagir G Ahmed
Department of Haematology, Aminu Kano Teaching Hospital, PMB 3452, Kano, Kano State
Source of Support: None, Conflict of Interest: None
Background Red cell distribution width (RDW) is raised in many diseases. Although disseminated intravascular coagulation (DIC)-triggering diseases such as sepsis and cancer are also associated with raised RDW, we believe that a superimposed DIC would further raise the RDW owing to fibrin deposition with attendant red cell fragmentation. Hence, we also believe that extensive fibrin deposition will lead to higher RDW (due to red cell fragmentation) and higher risk of multiorgan damage (MOD) (due to microvascular blockade) in DIC. This implies that high RDW in DIC would partly reflect the intensity of fibrin deposition and risk of MOD. We therefore hypothesize that RDW elevation may be associated with an increased risk of MOD in DIC. If our hypothesis is correct, DIC patients with MOD will have significantly higher RDW than their counterparts without MOD.
Materials and methods We performed a retrospective comparative analysis of the frequencies of organ damage with respect to RDW values among 96 DIC patients seen from 1996 to 2007 in two tertiary hospitals in Nigeria.
Results Patients with organ damage had higher mean values of RDW as compared with patients without organ damage (22.3 vs. 16.8%, P<0.05). Pearson’s analysis showed positive correlation between values of RDW and number of damaged organs among DIC patients with MOD (r=0.78, P<0.05).
Discussion This study suggests that high RDW values were associated with organ damage, and the number of damaged organs increased with rising values of RDW, as revealed by a significant positive correlation between RDW values and number of damaged organs. This correlation suggests that higher RDW values were associated with higher risk of MOD. These findings have validated our hypothesis that fibrin deposition, which is a major cause of MOD in DIC, would also cause red cell fragmentation and elevation of RDW. We conclude that high RDW is a risk factor for MOD in DIC, and RDW values may be of predictive significance in assessing the risk of MOD in patients with DIC.
Keywords: disseminated intravascular coagulation, multiorgan damage, red cell distribution width
|How to cite this article:|
Ahmed SG, Kagu MB, Ibrahim UA. Red cell distribution width as a predictive index for multiorgan damage in disseminated intravascular coagulation. Egypt J Haematol 2017;42:117-22
|How to cite this URL:|
Ahmed SG, Kagu MB, Ibrahim UA. Red cell distribution width as a predictive index for multiorgan damage in disseminated intravascular coagulation. Egypt J Haematol [serial online] 2017 [cited 2018 May 20];42:117-22. Available from: http://www.ehj.eg.net/text.asp?2017/42/3/117/217883
| Introduction|| |
Red cell distribution width (RDW) is a measure of variations of red cell size, and when expressed as coefficient of variation it has a normal range of 11.6–14.6% in adults . The RDW is raised in patients with impaired red cell synthesis in a variety of medical disorders ranging from haemoglobinopathies to nutritional anaemias and myelodysplastic syndromes, all of which are associated with primary or secondary dyserythropoiesis . Raised RDW is also a useful index of prediction, evaluation and prognostication for several mental and physical diseases ranging from depression to sepsis, cancer, diabetes and metabolic syndromes, as well as various diseases affecting the cardiovascular, renal, hepatic, pulmonary and endocrine systems ,,,,,,,,,,. The mechanisms underlying the elevation of RDW in these wide-ranging diseases have not been fully elucidated but are thought to be multifactorial, including infections, inflammations, oxidative stress, malnutrition and haemoglobin (Hb) glycosylation, all of which can lead to abnormal erythropoiesis, increased red cell viscosity, reduced red cell lifespan and in some cases reduced peripheral clearance of senescent red cells with prolongation of red cell lifespan ,,,,,,,,,,. Moreover, the RDW appears to be significantly affected by ageing, as increased risk of death was found to be associated with higher RDW values in elderly adults with and without age-associated diseases .
The RDW is also raised when red cells are fragmented into smaller schistocytes as seen in patients with a variety of thermal, mechanical, chemical and toxic red cell injuries . However, the classical red cell fragmentation syndromes are usually seen in thrombotic microangiopathy (TMA), which is typified by thrombotic thrombocytopaenic purpura and haemolytic uraemic syndrome in which intravascular fibrin leads to significant production of microangiopathic haemolysis and schistocytes . Because schistocytes are smaller than normal red cells, they tend to increase red cell size variations leading to elevation of RDW in TMA . Accordingly, elevated RDW has been shown to be an important diagnostic marker of TTP . In similarity with TMA, disseminated intravascular coagulation (DIC) is associated with activation of the coagulation cascade that leads to microvascular fibrin deposition . In fact, an earlier animal experimental evidence suggested that the excess fibrin strands in the microvasculature in DIC cause mechanical damage to red blood cells resulting in fragmentation and schistocyte formation that correlated with the degree of DIC . Moreover, data accrued from human patients suggested that red cell fragmentation was a common finding in DIC and examination of the blood film to detect schistocytes had been suggested as a rapid and useful test for the diagnosis of DIC . However, other studies had shown that although schistocytes were frequently seen in the blood of DIC patients, they usually occur in low numbers that were within or only modestly elevated above the normal reference range, and thus may not be used as reliable diagnostic markers for DIC ,. Hence, the literature review suggests that DIC is associated with red cell fragmentation and formation of schistocytes, but the extent and the clinical and diagnostic significance of these red cell changes in DIC patients have not been precisely determined.
Although many of the DIC-triggering diseases, especially sepsis, cancer and other inflammatory conditions, are also associated with elevation of RDW ,, we believe that a superimposed DIC would further raise the RDW owing to fibrin deposition with attendant microangiopathic red cell fragmentation ,,,,. Fibrin deposition in DIC also causes microvascular blockade, hypoperfusion and multiorgan damage (MOD) . Hence, we also believe that extensive fibrin deposition will lead to greater elevation of RDW (due to red cell fragmentation) and higher incidence of MOD (due to microvascular blockade) in patients with acute DIC. This implies that elevation of RDW values in DIC would partly reflect the intensity of fibrin deposition and the risk of MOD. We therefore hypothesize that RDW elevation may be associated with increased risk of MOD in patients with acute DIC. If our hypothesis is correct, DIC patients with MOD will have significantly higher elevation of RDW than their counterparts without MOD. To the best of our knowledge, the relationship between MOD and RDW among patients with DIC has not been previously studied. In order to test our hypothesis, we performed a retrospective comparative analysis of the frequencies of organ damage with respect to levels of RDW as seen among DIC patients in Nigeria.
| Materials and methods|| |
This is a retrospective study of patients with acute DIC diagnosed during an aggregate period of 24 years as seen in two northern Nigerian tertiary hospitals including University of Maiduguri Teaching Hospital, Maiduguri, northeast Nigeria (1996–2007), and State Specialist Hospital, Maiduguri, northeast Nigeria (1996–2007). The medical record of each patient was scrutinized to identify age, sex, clinical presenting features of DIC, underlying aetiological factors and the results of diagnostic tests and supporting investigations as determined at the time of diagnosis before administering any blood products. In each case the values of deranged coagulation parameters including low platelet count, elevated D-dimer, prolonged prothrombin time and low fibrinogen level were extracted and scored in accordance with the International Society of Haemostasis and Thrombosis (ISHT) for the diagnosis and severity assessment of DIC .
The patients studied in this report were cases of acute DIC, and each case was diagnosed on the basis of classical clinical features with haemorrhagic and/or thrombotic manifestations, identifiable underlying disorders known to be associated with DIC and a score of 5 or more based on the ISHT scoring system for DIC . The occurrence of clinical and laboratory indicators of organ damage as documented at the time of diagnosis in each case was identified and collated.
Patients with clinical features that were suggestive of acute DIC but lacked identifiable underlying disorders known to be associated with DIC or those who had a score of less than 5 on the basis of the ISHT scoring system for DIC were excluded from this study. Patients with missing or incomplete coagulation parameters for DIC scoring indices at diagnosis were also excluded. Patients who were transfused before laboratory evaluation procedures were excluded because of the possible effects of transfusion on coagulation and haematological parameters.
Laboratory tests were conducted by combination of manual and automated procedures. Platelet counts and RDW were performed as part of complete blood count procedure on EDTA anticoagulated blood using automatic blood analyzers . Prothrombin times were performed on citrated platelet poor plasma by automated coagulometers or by standard manual methods . Fibrinogen levels were determined on citrated plasma by automated coagulometers or by manual methods based on Clauss or enzyme-linked immunoabsorbant assays techniques . D-dimer levels were determined on fresh citrated plasma by automated analyzers or manually by using commercial kits for enzyme-linked immunoabsorbant assays or latex agglutination assays .
Diagnosis and identification of organ damage
Various types of organ damage that were diagnosed on the basis of documented clinical, laboratory and radiological evidence at the time of diagnosis of DIC were identified and enumerated. In this study, acute renal injury was diagnosed if the level of serum creatinine was elevated above 130 µmol/l ; acute hepatic injury was diagnosed if the levels of hepatic transaminases were elevated above 35 IU/l for alanine aminotransferase and above 42 IU/l for aspartate aminotransferase ; acute pulmonary injury was diagnosed if there were documented clinical features of respiratory distress and a pulse oxymetry SpO2 level lower than 95% with associated pulmonary opacities on chest radiographs ; and acute thrombotic musculoskeletal injury was diagnosed if there were documentations of gangrenous lesions in one or more toes, fingers or any part of patient limbs characterized by blackish discolouration of the overlying skin and radiological evidence of necrosis of the underlying tissues.
Ethics, data collation and analysis
This work was conducted with the approval of local institutional ethics committees. Demographic and clinical laboratory data including age, sex, aetiological causes of DIC and types of organ damage as determined at the time of diagnosis of DIC as obtained from the two centres of study were collated and merged. The frequencies of aetiological causes of DIC and organ damage were determined from the collated data. The mean values of Hb concentration, red cell indices (mean corpuscular volume, mean corpuscular Hb, mean corpuscular Hb concentration), leucocyte count, platelet count and RDW were compared between patients with and without organ damage based on the Student’s t-test, with P value less than 0.05 taken as statistically significant. In this study, RDW was recorded as coefficient of variation and the normal reference range was taken as 11.6–14.6% . The relationship between values of RDW and number of damaged organs among patients with MOD was assessed by Pearson’s correlation analysis where the coefficient of correlation, r, is considered significant at a P value less than 0.05. Statistical analyses were performed with SPSS software (version 19.0, IBM, SPSS Statistics; IBM, Chicago, Illinois, USA.).
| Results|| |
The demographic, clinical and laboratory parameters of 96 patients with acute DIC as documented at the time of diagnosis were retrospectively captured and analysed. The aetiological factors for the DIC are shown in [Table 1] wherein sepsis, malignancies and obstetric factors were predominant. Four types of acute organ damage, including renal, hepatic, pulmonary and musculoskeletal injuries were identified in this study. A total of 24 (25%) patients had one or more clinical and/or laboratory features of organ damage, as shown in [Table 2], wherein nine (37.5%), six (25%), five (20.8%) and four (16.7%) patients had renal, hepatic, pulmonary and musculoskeletal damage, respectively. The demographic and haematological parameters of patients with and without organ damage are shown in [Table 3]. There were no statistically significant differences with respect to mean age, sex ratio and mean values of leucocyte count, platelet count, mean corpuscular volume, mean corpuscular Hb and mean corpuscular Hb concentration between patients with and without organ damage (P>0.05). However, mean values of leucocyte and neutrophil counts were elevated in both patient categories, whereas mean values of eosinophil and platelet count were low in both patient categories. The mean values of Hb concentrations were low in both patient categories, but the values were lower in patients with organ damage as compared with patients without organ damage (7.1 vs. 9.5 g/dl, P<0.05). The mean values of RDW were elevated in both patient categories, but the values were higher in patients with organ damage as compared with patients without organ damage (22.3 vs. 16.8%, P<0.05). Pearson’s correlation analysis showed a significant positive correlation between values of RDW and number of damaged organs among patients with MOD (r=0.78, P<0.05), as shown in [Figure 1].
|Table 1 Pattern and frequencies of aetiological factors among 96 patients with disseminated intravascular coagulation|
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|Table 2 Clinical and laboratory profiles of 24 disseminated intravascular coagulation patients with one or more organ damage|
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|Table 3 Demographic and haematological parameters of 96 disseminated intravascular coagulation patients with and without organ damage|
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|Figure 1 Pearson’s correlation between values of RDW and number of damaged organs among 24 disseminated intravascular coagulation patients with organ damage.|
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| Discussion|| |
The spectrum of aetiological factors of DIC in our patients revealed a typical array of DIC-associated disorders ranging from infections to malignancies, obstetric disorders, trauma and envenomation, all of which are known to trigger DIC through a number of basic pathophysiologic mechanisms ranging from exogenous activation of coagulation (e.g. venoms) to endogenous activation of coagulation through inflammatory processes (e.g. sepsis) or through massive release of procoagulant materials into the bloodstream (e.g. products of conception) . However, an important limitation of this study is its relatively small sample size despite a fairly extended period of study in two Nigerian tertiary hospitals. We expected a larger sample size judging from the fact that many of the aetiological factors for DIC ranging from infection to trauma and obstetrics disorders are common problems in developing countries such as Nigeria, which is characterized by high prevalence of infectious diseases, high birth rates with inadequate maternal healthcare and poor road network . These small retrospective data may therefore simply be a tip of the iceberg with a significantly larger proportion of DIC patients dying at subtertiary healthcare centres before reaching tertiary health institutions such the hospitals from which the data of this study were accrued. Moreover, a number of patients were excluded from this study because they were inadequately investigated with limited haemostatic tests that were insufficient for the ISHT diagnostic and scoring system for DIC . Nonetheless, the high incidence of sepsis with sex ratio of less than 1 (female predominance) seen among our participants is consistent with the high rates of infections and obstetric/maternal disorders that are typically associated with tropical developing countries such as Nigeria .
The result of this study revealed that up to a quarter of our patients with acute DIC had laboratory or clinical evidence of one or more organ damage at the time of diagnosis. Comparative analysis of the haematological profiles of our cohort revealed that DIC patients with and without organ damage had comparatively similar low mean values of platelet count, which is a reflection of the basic pathophysiology of DIC in which thrombocytopaenia is a principal feature attributable to thrombin generation and thrombin-induced platelet aggregation . The mean values of leucocyte and neutrophil counts were elevated, whereas mean values of eosinophil count were low in both patient categories. These findings are the haematological manifestations of the underlying DIC-triggering diseases such as sepsis and cancer and other inflammatory conditions, which would cause inflammation-induced reactive neutrophilia and eosinopenia ,. Although the values of red cell indices were normal in both patient categories, the result of this study has also revealed that in comparison with their counterparts without organ damage DIC patients with organ damage had significantly higher RDW values. Previous studies suggest that microvascular blockade due to fibrin deposition is a major cause of MOD in DIC . Hence, we believe that the higher RDW values seen in our DIC patients with organ damage is due to greater fibrin deposition, which would cause both microvascular blockade  and microangiopathic haemolysis ,,,,, a situation that would explain the finding of lower Hb concentration seen among our patients with organ damage in comparison with their counterparts without organ damage. The lowest RDW value among our DIC patients with organ damage was 18.1%, as shown in the correlation depicted in [Figure 1], which suggests that RDW values of greater than 18% were associated with organ damage, and the number of damaged organs increased with rising values of RDW as revealed by a significant positive correlation between RDW values and number of damaged organs. This correlation suggests that higher RDW values were associated with higher risk of MOD. The findings of higher RDW in patients with organ damage coupled with the positive correlation between RDW values and number of damaged organs have validated our working hypothesis that fibrin deposition, which is a major cause of MOD in DIC, would also cause microangiopathic red cell fragmentation and elevation of RDW. Hence, high RDW is a risk factor for MOD in DIC patients.
| Conclusion|| |
DIC patients with organ damage had significantly higher RDW values than their counterparts without organ damage. Our results also suggest that RDW values of greater than about 18% were associated with MOD, and the number of damaged organs increases with rising values of RDW. This study suggests that high RDW is a risk factor for MOD in patients with DIC. Hence, RDW values may be of predictive significance in assessing the risk of MOD in patients with acute DIC. However, a larger prospective study is required to confirm the finding of this small retrospective study.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]