Alcohol, Substance use, Hematological changes
Alcohol is the most commonly used worldwide. Alcohol consumption is one of the leading causes of death. Chronic alcohol intake can interfere with various physiological, biochemical and metabolic processes of the blood cells and affect multiple organ systems. Alcohol use, especially in heavy drinkers, can cause different metabolic derangements. Haematological adverse effects of acute and chronic alcohol use result from both direct and indirect effects [4,5]. The direct consequences include toxicity to the blood-forming organs (viz. bone marrow); the blood cell precursors; and the mature Red Blood Cells (RBC’s), White Blood Cells (WBC’s), and platelets, resulting in fewer than-normal or non-functional mature blood cells.
Alcohol’s indirect effects include metabolic or physiological alterations resulting in liver disease and nutritional deficiencies such as folate deficiencies that impair the production and function of various blood cells [4-6]. Folate deficiency also has an important role in the pathogenesis and progression of alcohol-related liver disease . Moreover, Liver damage secondary to alcohol abuse also impacts red blood cells and the hemostatic mechanisms. These direct and indirect effects of alcohol can result in serious medical complications among alcohol abusers. For instance, anaemia resulting from diminished RBC production and impaired RBC metabolism and function causes fatigue, shortness of breath, light headedness, and even reduced mental capacity and abnormal heartbeats in alcoholics. It has been found that alcohol interferes with the production and function of white blood cells. The number of WBC’s decreases (especially neutrophils) which increases the risk of serious infection. Also, the platelet (PLT) production gets impaired resulting in interference with blood clotting. This may lead to symptoms ranging from nose bleeding to bleeding in the brain (i.e., hemorrhagic stroke). Finally, alcohol-induced abnormalities in the plasma proteins, required for blood clotting can lead to the formation of blood clots (i.e., thrombosis) . Evidence is there to suggest that alcohol abuse can cause bone marrow suppression, or ethanol has cytotoxic effects. These includes myelosuppression that is accompanying with slight reduction in all blood cells, blood loss from gastrointestinal tract, malnutrition etc . Among the mechanisms explored for the effect of alcohol is the formation of adducts by acetaldehyde with cellular proteins . These altered proteins have been postulated to evoke an immune reaction as evidenced by the presence of IgM and IgG antibodies against them. Studies suggest that consumption of alcohol causes changes of Complete Blood Counts (CBC). A study from India shows significant reductions of haemoglobin, RBC, WBC, haematocrit and significant elevations in MCV and MCH among alcoholics . Another study from, India, compared the changes in the complete blood count in 30 young male subjects between 20-40 years of age group who consumed two to three units of alcohol on a daily basis with abstainers of the same age group . The findings suggest that drinking of alcohol even for a short or moderate duration can affect various haematological parameters like platelet count and Mean Corpuscular Volume (MCV). Furthermore, another study from North India examined the haematological profile of alcohol dependent subjects . The results showed an increase in erythrocyte Mean Cell Volume (MCV), Mean Corpuscular Haemoglobin (MCH), and a decreased mean value of RBC, total leucocyte and platelet counts, particularly among those with higher amount of alcohol consumption. In another study from South India the haematological parameters were examined in male alcoholics. The results were in line with the earlier report which suggested that the MCV was increased in the patients with alcohol dependence either co-morbid with tobacco dependence or without, compared to normal subjects . Recently, a cross-sectional study has been published in which comparison of haematological parameters between alcoholics and non-alcoholics were done. The findings indicated that mean RBC count, mean MCH, MCHC were normal among the non-alcoholic group and decreased among moderate alcoholics and more so with severe alcoholics and a similar type of result was also seen with total count and platelet count . A study from Japan attempted to characterise the change in the white blood cell counts with varying alcohol consumption levels as it has been seen that lower number of white blood cells has been associated with a decreased risk for chronic heart disease . The common abnormalities that are associated with alcohol abuse with respect to duration of alcohol abuse and the quantity of alcohol consumed are anemia, leukopenia and thrombocytopenia . Several studies have tried to explain the mechanism through which alcohol causes these changes in blood parameters. Anemia may be caused by a patient’s poor nutritional status coupled with poorer access to health care. This resulted in chronic infections causing anemia of chronic disease, through blood loss from gastrointestinal bleeds, through splenic sequestration and destruction of cells in hyper-splenic from portal hypertension [16,17]. The findings suggest that the development of megaloblastic haematopoiesis in alcoholics is due to the induction of folate deficiency. Besides folate depletion, direct toxic effect of alcohol on erythroid precursors is reflected by the presence of normal plasma and erythrocyte folate levels in several patients with megaloblastic change. Another important effect of alcohol is in haematopoiesis in the marrow. Ringed side oblasts are seen in the marrow and the marrow might be hypoplastic or even aplastic . A finding that precedes anemia is macrocytosis, the mechanism of which is not known . This result in cell sizes ranging from 100-110 falls this finding has to be differentiated from megaloblastic anemia in which cell sizes generally exceed that seen in alcohol use. The poor immunity to infections in alcohol dependent subjects may be the result of both the decrease in neutrophil number as well as faulty functioning . The decreased counts may be caused due to marrow hypoplasia or hypersplenism. The effects on the blood platelets are similar with effect on both thrombocyte formation as well as functioning. The platelet count rarely falls below 10,000/mm3. Abstaining from alcohol results in a rebound thrombocytosis in the first two weeks, counts may reach up to 600,000/mm3 . Alcohol use has also been clearly observed with increased iron stores specially in the liver resulting in an iron overload state . This adds to the oxidative stress that plays a part in the development of hepatic cirrhosis.
The link between white blood cells, platelets and atherosclerosis is well established, but do endocannabinoids play a role? There has been little work in this area, but the first clue came from Steffens et al. (2005), who reported that low doses of THC acting via CB2 receptors caused a reduction in the development of atherosclerotic plaques in a murine knockout model of atherogenesis. These effects appeared via suppression of macrophage chemotaxis. Whether endocannabinoids play a role in atherosclerosis remains to be determined, but a recent study has shown that low levels of palmitoylethanolamide (PEA) may protect low-density lipoprotein (LDL) against oxidation, which is a feature of atherogenesis (Zolese et al., 2005). By contrast, higher concentrations of PEA appear to promote the oxidation.
Endocannabinoids are blood borne and may also be secreted by the endothelium. Accordingly, there has been interest in the interactions between (endo)cannabinoids and blood cells. There is certainly evidence that (endo)cannabinoids may promote platelet activation, indicating that they may be thrombogenic. Platelets are involved both in the metabolism and release of endocannabinoids, and so it is possible that their circulating levels may be regulated by platelets. This process is altered in disease states such that platelet-derived endocannabinoids contribute towards hypotension in cardiovascular shock. Not only may endocannabinoids regulate platelet function and possibly lead to thrombogenesis, but they may also influence haematopoiesis. Given these emerging roles, the aim of this review is to examine the interactions between cannabinoids and blood.
The role of platelets in endocannabinoid reuptake and metabolism
Although the precise role platelets play in the regulation of circulating levels of endocannabinoids is unclear, an interesting observation has been reported by Cupini et al. (2005). In their paper, they argue that anandamide might be involved in modulating pain associated in migraine. In their investigation, they examined the metabolism of anandamide in a number of patients with migraine. Intriguingly, they reported that the uptake of anandamide and FAAH activity were both upregulated in platelets from female, but unaffected in male patients with migraine. From these findings, they suggested that sex-related differences might mean that in female patients with migraine, the circulating levels of anandamide were reduced by platelets and that this might reduce the pain threshold and contribute towards the pathophysiology of migraine. Although it should be noted that Akerman et al. (2004) have proposed that anandamide may, in fact, be involved in or modulate the neurovascular mechanisms in migraine, depending whether it acts via transient release potential family vanilloid type-1 receptors or cannabinoid CB1 receptors. These findings would suggest that in the central nervous system, endocannabinoids contribute towards the symptoms of migraine.
The cardiovascular actions of cannabinoids and endocannabinoids have been extensively reviewed (Randall et al., 2004; Pacher et al., 2006), but far less is known about their actions on blood. There is evidence that endocannabinoids may be produced in the endothelium (Mechoulam et al., 1998; Maccarrone et al., 2002; Gauthier et al., 2005) and blood cells may themselves act as a source; but what is the relationship between endocannabinoids and the haematological system?
Not only may platelets be activated by endocannabinoids, although at very high concentrations, but they may also be involved in metabolic conversion. Edgemond et al. (1998) reported that human platelets convert anandamide via 12-lipoxygenase to 12(S)-hydroxyeicosatetraenoylethanolamide (12(S)-HAEA). This metabolite is pharmacologically active at both CB1 and CB2 receptors with similar affinities to anandamide. Furthermore, 12(S)-HAEA was shown to be relatively resistant to metabolism by FAAH, and the authors proposed that the platelet-dependent conversion was a means by which the activity of endogenous cannabinoid ligands might be prolonged in the circulation.
This condition can be very painful — here’s how CBD may be able to help.
In 100 mL of hemp seed oil, there’s approximately 8 mg of iron.
Some examples of anemia caused by premature red blood cell destruction include:
It’s important to understand what type of anemia you have.