Low-Dose Aspirin Plus Low-Dose Warfarin May be Life-Saving Treatment Regimens in Cases with Severe Chronic Obstructive Pulmonary Disease

Special Article: Cryoglobulinemias

J Blood Disord. 2023; 10(3): 1081.

Low-Dose Aspirin Plus Low-Dose Warfarin May be Life-Saving Treatment Regimens in Cases with Severe Chronic Obstructive Pulmonary Disease

Mehmet Rami Helvaci1*; Valeria Pappel2; Kubra Piral2; Mehpare Camlibel3; Huseyin Sencan1; Ramazan Davran4; Mustafa Yaprak1; Abdulrazak Abyad5; Lesley Pocock6

1Specialist of Internal Medicine, MD, Turkey

2Manager of Writing and Statistics, Turkey

3Specialist of Emergency Medicine, MD, Turkey

4Specialist of Radiology, MD, Turkey

5Middle-East Academy for Medicine of Aging, MD, Lebanon

6Medi-WORLD International, Australia

*Corresponding author: Mehmet Rami Helvaci, MD Specialist of Internal Medicine, 07400, ALANYA, Turkey. Tel: 00-90-506-4708759 Email: mramihelvaci@hotmail.com

Received: September 01, 2023 Accepted: October 23, 2023 Published: October 30, 2023

Abstract

Background: Sickle Cell Diseases (SCDs) are inborn and catastrophic processes on vascular endothelium, particularly at the capillaries.

Methods: All patients with the SCDs were included.

Results: We studied 222 males and 212 females with similar mean ages (30.8 vs 30.3 years, p>0.05, respectively). Beside Chronic Obstructive Pulmonary Disease (COPD) (25.2% vs 7.0%, p<0.001), smoking (23.8% vs 6.1%, p<0.001), alcohol (4.9% vs 0.4%, p<0.001), transfused red blood cells (RBCs) in their lives (48.1 vs 28.5 units, p=0.000), disseminated teeth losses (5.4% vs 1.4%, p<0.001), ileus (7.2% vs 1.4%, p<0.001), cirrhosis (8.1% vs 1.8%, p<0.001), leg ulcers (19.8% vs 7.0%, p<0.001), digital clubbing (14.8% vs 6.6%, p<0.001), coronary heart disease (CHD) (18.0% vs 13.2%, p<0.05), chronic renal disease (CRD) (9.9% vs 6.1%, p<0.05), and stroke (12.1% vs 7.5%, p<0.05) were all higher, and autosplenectomy (50.4% vs 53.3%, p<0.05) and mean age of mortality were lower in males, significantly (30.2 vs 33.3 years, p<0.05).

Conclusion: The hardened RBCs-induced capillary endothelial damage initiates at birth, and terminates with multiorgan failures even at childhood in the SCDs. Parallel to the COPD, all of the atherosclerotic risk factors or consequences including smoking, alcohol, disseminated teeth losses, ileus, cirrhosis, leg ulcers, digital clubbing, CHD, CRD, and stroke were higher, and autosplenectomy and mean age of mortality were lower in males which can not be explained by effects of smoking and alcohol alone at the younger age. So COPD may have an atherosclerotic background, and low-dose aspirin plus low-dose warfarin may be life-saving treatment regimens in severe COPD.

Keywords: Sickle cell diseases; Hardened red blood cells; Capillary endothelial edema; Sudden deaths; Chronic obstructive pulmonary disease; Low-dose warfarin; Low-dose aspirin

Introduction

Chronic endothelial damage may be the main underlying cause of aging and death by causing end-organ failures [1]. Much higher Blood Pressures (BPs) of the afferent vasculature may be the chief accelerating factor by causing recurrent injuries on vascular endothelium. Probably, whole afferent vasculature including capillaries are mainly involved in the destructive process. Thus the term of venosclerosis is not as famous as atherosclerosis in the literature. Due to the chronic endothelial damage, inflammation, edema, and fibrosis, vascular walls thicken, their lumens narrow, and they lose their elastic natures which eventually reduce blood flow to the terminal organs, and increase systolic and decrease diastolic BPs further. Some of the well-known accelerating factors of the harmful process are physical inactivity, sedentary lifestyle, animal-rich diet, smoking, alcohol, overweight, chronic inflammations, prolonged infections, and cancers for the development of terminal consequences including obesity, Hypertension (HT), Diabetes Mellitus (DM), cirrhosis, Chronic Obstructive Pulmonary Disease (COPD), Coronary Heart Disease (CHD), Chronic Renal Disease (CRD), stroke, Peripheric Artery Disease (PAD), mesenteric ischemia, os teoporosis, dementia, early aging, and premature death [2,3]. Although early withdrawal of the accelerating factors can delay terminal consequences, after development of obesity, HT, DM, cirrhosis, COPD, CRD, CHD, stroke, PAD, mesenteric ischemia, osteoporosis, aging, and dementia-like end-organ insufficiencies, the endothelial changes can not be reversed due to their fibrotic natures, completely. The accelerating factors and terminal consequences of the harmful process are researched under the titles of metabolic syndrome, aging syndrome, and accelerated endothelial damage syndrome in the literature [4-6]. Similarly, Sickle Cell Diseases (SCDs) are highly destructive processes on vascular endothelium initiated at birth, and terminated with an advanced atherosclerosis-induced end-organ failures in much earlier ages of life [7,8]. Hemoglobin S causes loss of elastic and biconcave disc shaped structures of Red Blood Cells (RBCs). Probably loss of elasticity instead of shape is the major problem because sickling is rare in peripheric blood samples of the patients with associated Thalassemia Minors (TMs), and human survival is not affected in hereditary spherocytosis or elliptocytosis. Loss of elasticity is present even at birth, but exaggerated with inflammations, infections, and emotional stress of the body. The sickled or just hardened RBCs-induced chronic endothelial damage, inflammation, edema, and fibrosis terminate with disseminated tissue hypoxia all over the body [9]. As a difference from other causes of chronic endothelial damage, SCDs keep vascular endothelium particularly at the capillaries which are the actual distributors of the sickled or just hardened RBCs into the tissues [10,11]. The sickled or just hardened RBCs-induced chronic endothelial damage builds up an advanced atherosclerosis in much earlier ages of life. Vascular narrowings and occlusions-induced tissue ischemia and end-organ failures are the terminal results, so the life expectancy is decreased by 25 to 30 years for both genders in the SCDs [8].

Material and Methods

The clinical study was performed in Medical Faculty of the Mustafa Kemal University between March 2007 and June 2016. All patients of the SCDs were included. The SCDs are diagnosed with the hemoglobin electrophoresis performed by means of High Performance Liquid Chromatography (HPLC). Smoking and alcohol habits, acute painful crises per year, transfused units of RBCs in their lives, leg ulcers, stroke, surgical operations, Deep Venous Thrombosis (DVT), epilepsy, and priapism were learnt. Cases with a history of one pack-year were accepted as smokers, and one drink-year were accepted as drinkers. A complete physical examination was performed by the Same Internist, and patients with disseminated teeth losses (<20 teeth present) were detected. Patients with an acute painful crisis or any other inflammatory process were treated at first, and the laboratory tests and clinical measurements were performed on the silent phase. A check up procedure including serum iron, iron binding capacity, ferritin, creatinine, liver function tests, markers of hepatitis viruses A, B, and C, marker of human immunodeficiency virus, a posterior-anterior chest x-ray film, an electrocardiogram, a Doppler echocardiogram both to evaluate cardiac walls and valves, and to measure systolic BPs of pulmonary artery, an abdominal ultrasonography, a venous Doppler ultrasonography of the lower limbs, a Computed Tomography (CT) of brain, and a Magnetic Resonance Imaging (MRI) of hips was performed. Other bones for avascular necrosis were scanned according to the patients’ complaints. So avascular necrosis of bones was diagnosed via MRI [12]. Associated TMs were detected with serum iron, iron binding capacity, ferritin, and hemoglobin electrophoresis performed via HPLC, becuase the SCDs with associated TMs show a milder clinic than the Sickle Cell Anemia (SCA) (Hb SS) alone [13]. Systolic BPs of the pulmonary artery of 40 mmHg or higher are accepted as Pulmonary Hypertension (PHT) [14]. The criterion for diagnosis of COPD is a post-bronchodilator forced expiratory volume in one second/forced vital capacity of lower than 70% [15]. Acute Chest Syndrome (ACS) is diagnosed clinically with the presence of new infiltrates on chest x-ray film, fever, cough, sputum, dyspnea, or hypoxia [16]. An x-ray film of abdomen in upright position was taken in patients with abdominal distention or discomfort, vomiting, obstipation, or lack of bowel movement, and ileus is diagnosed with gaseous distention of isolated segments of bowel, vomiting, obstipation, cramps, and with the absence of peristaltic activity. CRD is diagnosed with a persistent serum creatinine level of 1.3 mg/dL or greater in males and 1.2 mg/dL or greater in females. Cirrhosis is diagnosed with physical examination, laboratory parameters, and ultrasonographic findings. Clubbing is diagnosed with the ratio of distal phalangeal diameter to interphalangeal diameter of greater than 1.0, and with the presence of Schamroth’s sign [17,18]. An exercise electrocardiogram is performed in cases with an abnormal electrocardiogram and/or angina pectoris. Coronary angiography is performed for the cases with exercise electrocardiogram positivity. So CHD is diagnosed either angiographically or with the Doppler echocardiographic findings as movement disorders in the cardiac walls. Rheumatic heart disease is diagnosed with the echocardiographic findings, too. Stroke is diagnosed by the CT. Sickle cell retinopathy is diagnosed with ophthalmologic examination in cases with visual complaints. Mann-Whitney U test, Independent-Samples t test, and comparison of proportions were the methods of statistical analyses.

Results

The study included 222 males and 212 females with similar ages (30.8 vs 30.3 years, p>0.05, respectively). Prevalences of associated TMs were similar in both genders, too (72.5% vs 67.9%, p>0.05, respectively). Smoking (23.8% vs 6.1%) and alcohol (4.9% vs 0.4%) were higher in males (p<0.001 for both) (Table 1). On the other hand, transfused RBCs in their lives (48.1 vs 28.5 units, p=0.000), disseminated teeth losses (5.4% vs 1.4%, p<0.001), COPD (25.2% vs 7.0%, p<0.001), ileus (7.2% vs 1.4%, p<0.001), cirrhosis (8.1% vs 1.8%, p<0.001), leg ulcers (19.8% vs 7.0%, p<0.001), digital clubbing (14.8% vs 6.6%, p<0.001), CHD (18.0% vs 13.2%, p<0.05), CRD (9.9% vs 6.1%, p<0.05), and stroke (12.1% vs 7.5%, p<0.05) were all higher, and autosplenectomy (50.4% vs 53.3%, p<0.05) and mean age of mortality were lower in males (30.2 vs 33.3 years, p<0.05) (Table 2). Beside that the mean ages of terminal consequences were shown in Table 3.