Cardiovascular & Haematological Disorders - Drug Targets - Volume 20, Issue 3, 2020

Background: It is important to discard those practices that do not add value. As a result, several initiatives have emerged. All of them try to improve patient safety and the use of health resources. Purpose: To present a compendium of "do not do recommendations" in the context of hemophilia. Methods: A review of the literature and current clinical guidelines has been made, based on the best evidence available to date. Results: The following 13 recommendations stand out: 1) Do not delay the administration of factor after trauma; 2) do not use fresh frozen plasma or cryoprecipitate; 3) do not use desmopressin in case of hematuria; 4) do not change the product in the first 50 prophylaxis exposures; 5) do not interrupt immunotolerance; 6) do not administer aspirin or NSAIDs; 7) do not administer intramuscular injections; 8) do not do routine radiographs of the joint in case of acute hemarthrosis; 9) Do not apply closed casts for fractures; 10) do not discourage the performance of physical activities; 11) do not deny surgery to a patient with an inhibitor; 12) do not perform instrumental deliveries in fetuses with hemophilia; 13) do not use factor IX (FIX) in patients with hemophilia B with inhibitor and a history of anaphylaxis after administration of FIX. Conclusion: The information mentioned previously can be useful in the management of hemophilia, from different levels of care. As far as we know, this is the first initiative of this type regarding hemophilia.

HIV-positive patients have a 60- to 200-fold increased incidence of Non-Hodgkin Lymphomas (NHL) because of their impaired cellular immunity. Some NHL are considered Acquired Immunodeficiency Syndrome (AIDS) defining conditions. Diffuse large B-cell Lymphoma (DLBC) and Burkitt Lymphoma (BL) are the most commonly observed, whereas Primary Effusion Lymphoma (PEL), Central Nervous System Lymphomas (PCNSL), Plasmablastic Lymphoma (PBL) and classic Hodgkin Lymphoma (HL) are far less frequent. Multicentric Castleman disease (MCD) is an aggressive lymphoproliferative disorder highly prevalent in HIV-positive patients and strongly associated with HHV-8 virus infection. In the pre-Combination Antiretroviral Therapy (CART) era, patients with HIV-associated lymphoma had poor outcomes with median survival of 5 to 6 months. By improving the immunological status, CART extended the therapeutic options for HIV positive patients with lymphomas, allowing them to tolerate standard chemotherapies regimen with similar outcomes to those of the general population. The combination of CART and chemotherapy/ immuno-chemotherapy treatment has resulted in a remarkable prolongation of survival among HIVinfected patients with lymphomas. In this short communication, we briefly review the problems linked with the treatment of lymphoproliferative diseases in HIV patients. Combination Antiretroviral Therapy (CART) not only reduces HIV replication and restores the immunological status improving immune function of the HIV-related lymphomas patients but allows patients to deal with standard doses of chemotherapies. The association of CART and chemotherapy allowed to obtain better results in terms of overall survival and complete responses. In the setting of HIVassociated lymphomas, many issues remain open and their treatment is complicated by the patient’s immunocompromised status and the need to treat HIV concurrently.

Nowadays Coronavirus Disease 2019 (Covid-19) is increasing mortality all over the world mercilessly. We are learning almost every day about its new symptoms and that it mutates quickly. This disease has tied us up and made us desperate. The death rate from this disease has increased in patients who had pre-existing medical conditions, especially cardiovascular ones, by eliminating the angiotensin-converting enzyme (ACE)-2 receptor in the lungs. Also, ACE1 and angiotensin receptor blockers (ARB) may stimulate ACE2 expression and worse the prognosis. Intravenous infusions of ACEIs and ARBs in experimental animals increase the number of ACE2 receptors. Therefore, it may be one of the reasons that COVID-19 infects the cells of patients treating hypertension. However, most of the congress of cardiology do not recommend to discontinue these anti-hypertensive drugs. Therefore, this brief report evaluates Covid-19 in the view of cardiovascular diseases taking into account current reports and suggests some possible solutions to keep the virus under control.

Objective: Development of inhibitors in hemophilia A and B comprise significant challenge for patients, hematologists, and health provider systems. It has recommended by the World Federation of Hemophilia (WFH) to check inhibitors every 3-4 months. The incidence of inhibitor in hemophilia B is lower than hemophilia A. Here, it tried to unravel whether the detection of inhibitors in hemophilia B neglected compared to hemophilia A or not? Methods: A comprehensive review carried out using six international and local medical search engines on published contributions about inhibitors in hemophilia A and B in Iran. Results: From 699 titles, 12 relevant papers were selected. The mean of factor VIII inhibitors in hemophilia A was 14.8%. The mean of factor IX inhibitors in hemophilia B was 6%. The minimum and maximum reported percentages of factor VIII inhibitors were 4% and 19.6%, while the minimum and maximum of reported percentages of factor IX inhibitors were 0% and 11.8%, respectively. The inhibitors in hemophilia A had reported in 6 papers. One paper had covered the inhibitors in hemophilia B. There were five papers on inhibitors in both hemophilia A and B. The comparison between the reported patients showed that 3020 patients with hemophilia A and 314 patients with hemophilia B had studied. Conclusion: Consistent with the lower frequency of hemophilia B and the lower development of inhibitors in hemophilia B compared to hemophilia A, it was concluded that hemophilia B had not neglected in Iran. It seems to be rational that each country, check rates of detection of inhibitors in hemophilia B to identify whether it has neglected or not.

Objectives: In this study, we aimed to assess the value of admission time CBC parameters in predicting post-primary PCI corrected TIMI frame count. Background: Recent years have witnessed a large series of studies evaluating different laboratory variables to predict no-reflow phenomenon following primary PCI (PPCI) in patients with STEMI. However, a general agreement about the most reliable predictor of the no-reflow phenomenon is challenging and also intriguing. Methods: The current study concluded 208 consecutive patients who underwent primary PCI for ST-Elevation Myocardial Infarction (STEMI) from January 2014 to February 2016. Blood samples were obtained after taking ECG. Complete blood samples were collected and analyzed within 5 minutes from sampling. Post-PCI corrected Thrombolysis in Myocardial Infarction (TIMI) frame count was determined by one interventional cardiologist blinded to patients’ clinical data. The correlation between admission time blood parameters and post-primary PCI corrected TIMI frame count in patients with STEMI were assessed. Results: Corrected TIMI frame count was positively correlated with WBC count (R: 0.18, P-value: <0.01), neutrophil count (R: 0.34, P-value: <0.01), and platelet count (R: 0.23, P-value: <0.01) and negatively correlated with lymphocyte count (R: -0.2, P-value: <0.01). Multiple linear regression results demonstrated that corrected TIMI frame count was positively correlated with neutrophil count (P < 0·001) and platelet count (P < 0·001) and negatively correlated with lymphocyte count (p=0.004). Conclusion: High counts of WBC, neutrophil, and platelet and low count of lymphocyte may be predictors of no-reflow in STEMI patients undergoing PPCI. The clinical significance of such predictive parameters becomes clear as we consider the treatment approach in STEMI patients. Appropriate risk stratification leads to better treatment planning and allocation of resources.

Background & Objective: Age-dependent Organophosphates (OPs) toxicity is a controversial topic. The present study was designed to investigate the effect of the sub-acute exposure to diazinon (DZN), one of the main OPs insecticides, on the hematological alterations in adult and aged male rats. Methods: For the aim of this approach, the adult and aged rats were administered with DZN (15 mg/kg, orally) for 4 weeks. Then, the blood samples were collected from the retro-orbital sinus for measuring red blood cell (RBC), hemoglobin (Hb), hematocrit (Hct), platelets (PLT), MCV (mean corpuscular volume), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin (MCHC). Results: The obtained results indicated that DZN significantly decreased RBCs (4.93 ± 0.41), Htc (28.12 ± 1.21), Hb (10.31 ± 0.36), MCHC (30.51 ± 2.04), MCV (62.86 ± 2.58), and PLT (265.6 ± 34.81) values in the adult and aged rats versus the age-matched control rats. Moreover, RBC, Hb, and Htc levels decreased significantly in the aged rats versus adult rats. However, no significant differences were observed between MCHC, MCV, and PLT levels in adult and aged rats. Moreover, the MCH concentration did not change in any group. Additionally, DZN did not deteriorate the hematological alterations in the aged rats versus adult rats. Conclusion: the present study showed that the toxicity of DZN is not associated with age. However, more studies should be conducted to confirm this finding.

Background and Objectives: The relationship between vascular damage and diabetes mellitus was exploited using avocado seed extracts. The purpose of the study was to understand the therapeutic relevance of glycosides compared to standard vascular and anti-diabetic drugs. Constituent Avocado Seed Glycosides (ASG) were analysed and administered to rats with Diabetes-Induced Vascular Damage (DIVD). Methods: The rats were first administered with streptozotocin and screened after seven days for alterations in blood glucose, insulin, vascular cell adhesion molecule (VCAM-1), Von Willebrand factor (VWF), Renin-Angiotensin-Aldosterone System (RAS), eNOx, and endothelin-1 (ET-1). Only rats that satisfied these criteria were recruited and treated with either glibenclamide, met.su + losart, or 200 mg/kg body weight ASG for 28 days. Results: There was an abundance of digitoxin (13.41 mg/100g), digoxin (17.98 mg/100g), avicularin (165.85 mg/100g), and hyperoside (282.51 mg/100g). ASG or met.su + losart exhibited slight modulatory properties on glucose homeostasis. Rats with DIVD showed elevated renin, angiotensin, VCAM-1 and Lp-PLA2 levels but slightly decreased with glibenclamide treatment and normalized with ASG or met.su + losart administration. All treatments normalized Hcy levels. DIVD caused the overproduction of CnT, LDH, Crt-K, LDL-c, TG, and TC and suppressed HDL-c but was completely normalized by the ASG. Water intake remained altered in treated rats. Conclusion: The ASG had no relevant effect on glucose homeostasis during DIVD but showed significant vasoprotective properties.

Objectives: Thalassemia major (TM) is one of the most common blood disorders with a high mortality rate due to cardiovascular disease. Vitamin D deficiency has been suggested to implicate in cardiac abnormalities. In this prospective study, we aimed to investigate the relationship between serum levels of vitamin D and tissue Doppler (TD) echocardiographic indices in thalassemia major patients. Methods: A total of 81 TM patients, including 56 females and 25 males, with a mean age of 27.5± 6.8 years, were enrolled consecutively. Serum levels of vitamin D and other biomedical parameters were measured. Then, all patients were subjected to TD echocardiography. Correlations between the serum parameters and systolic and diastolic indices were examined. Results: The serum level of vitamin D was correlated with systolic and diastolic indices such as the EF (r= 0.33, P= 0.003) and TD Imaging (TDI)-lateral (r= 0.31, P= 0.005). However, no correlations were observed between vitamin D deficiency and the LV septal and posterior wall thickness, TDIseptal, tricuspid regurgitation peak gradient (TRPG), pulmonary artery systolic pressure (PASP), deceleration time (DT), and propagation velocity (PVcm/s) indices. The results revealed also no linear correlations between serum vitamin D and albumin (r= -0.17, P= 0.06), ALP (r= -0.12, P= 0.14), T4 (r= -0.11, P= 0.16), as well as TSH (r= -0.10, P= 0.19). Conclusion: It seems that vitamin D deficiency in patients with TM is associated with systolic but not diastolic dysfunctions, possibly as consequences of related biochemical abnormalities.

Background: Acute coronary syndrome (ACS) is one of the leading causes of mortality worldwide and is characterized by unstable angina or acute myocardial infarction. The aim of this study is to evaluate the clinical characteristics of patients who died of ACS. Methods: In this cross-sectional study, 1000 patients presenting ACS were included. Data and records of these patients were evaluated for parameters such as; deceased status, age, gender, diagnosis, ECG, common complaints, associated risk factors, Killip class, pulse, blood pressure, geographic setup (urban or rural), complications and season in which the disease was presented. Statistical analysis was performed on the data obtained using SPSS-win software. Results: The mortality rate among ACS patients in our study was 7.1%. Of these patients, AMI was the most prevalent diagnosis and chest pain was the most common complaint. Furthermore, low blood pressure, advanced age, increased pulse rate and fall/winter season were associated with the increased risk of mortality. ST deviation was the most seen ECG finding and most of the mortalities were within the 24 hours of admission. Conclusion: Our study reports risk factors associated with mortality in ACS patients. Advanced and timely therapeutic measurements are likely to reduce the incidence of mortality in these patients.

Background: Dual antiplatelet therapy (DAPT) remains the cornerstone management for the prevention of acute stent thrombosis after percutaneous intervention (PCI). Situations mandating early interruption of DAPT carry a high risk of ischemic complications. Perioperative bridge therapy using Cangrelor, an intravenous P2Y2 inhibitor, may offer a potential solution. Unfortunately, evidence for its use in non-cardiac procedures is limited. Methods: Our protocol demonstrates successful off-label use of IV Cangrelor bridge therapy in a non-cardiac surgery patient. We describe a case of a 77-year old male; triple therapy with Aspirin, Apixaban, and Ticagrelor for recent drug-eluting stent placement required immediate surgical resection of stage I colonic adenocarcinoma. Results: Cangrelor bridge therapy was utilized both preoperatively and postoperatively without ischemic or bleeding complications. The patient tolerated exploratory laparoscopic colectomy with minimal bleeding and good post-op recovery. Conclusion: Minimizing the interruption of DAPT therapy in high-risk patients is achievable. However, careful planning with a team-based approach involving surgeons, cardiologists and pharmacists, along with close clinical follow-up and vigilant management of anti-platelet therapy is recommended.

Stroke following percutaneous trans-septal mitral commissurotomy (PTMC) is an unusual complication that could significantly affect the quality of life of the patients, particularly the young and active ones. We present a middle-aged woman who experienced stroke following PTMC and successfully treated with thrombolytic therapy regarding the potential adverse effects of this type of therapy. Also, we present a simple novel stepwise clinical approach for PTMC-related stroke.

A significant percentage of B-cell lymphomas are characterized by bone marrow involvement (BMI) at diagnosis. In most cases, there is a concordance between the type of lymphoma present in the lymph node and the lymphoma present in the bone marrow. Herein, we presented a sixty-seven years old female patient, who was diagnosed with High-Grade B-cell Lymphoma (HGBL) in the bone marrow, while simultaneously, in the peripheral lymph node, the presence of Follicular Lymphoma (FL) was noted. The patient was presented to the hospital with spontaneous tumor lysis syndrome, a finding compatible with the aggressive course of the HGBL. To our knowledge, this is the first case of the co-existence of HGBL in the bone marrow and FL in a lymph node, which might be attributed to merely a coincidence or to the transformation of the cells in the preferable milieu of the bone marrow.