Israel Medical Association Journal

Background: Low-risk venous thromboembolism (VTE) patients are advised to be discharged from the emergency department (ED) on direct oral anticoagulants (DOACs) treatment. There is no data on whether this recommendation is followed in Israel.

Objectives: To characterize newly diagnosed VTE patients who were discharged from the ED, their anticoagulation treatment at the ED, the recommended discharge protocol, and patient adherence.

Methods: We conducted a retrospective cohort study, which included all newly diagnosed VTE patients who were discharged from the ED. Collected data included demographic and clinical background; anticoagulation treatment at the ED, recommended discharge protocol and its subsequent adherence, patient subsequent, recommended hematological evaluation, and adverse events.

Results: The study group included 443 patients, 89% with deep vein thrombosis (DVT). Approximately three-quarters were treated with anticoagulants in the ED, 98% with enoxaparin. At discharge, anticoagulants were recommended for all; 49% continued enoxaparin, 47% DOACs, and 4% warfarin. After 4 weeks, 67% were treated with DOACs, 22% with enoxaparin, 5% with warfarin. Approximately 6% discontinued all treatment. After 12 weeks, 90% of the patients who were taking DOACs adhered to the protocol, whereas only 70% and 50% among the enoxaparin and warfarin users, respectively, did. Only 56% were referred for hematological evaluation. The 12-week rate of adverse reactions was approximately 2%. The use of DOACs and the recommendation for further hematological evaluation increased over time.

Conclusions: Clinician training regarding discharge of VTE patients from the ED should continue.

Background: Factor VII (FVII) deficiency is characterized by normal activated partial thromboplastin time (aPTT) and prolonged prothrombin time (PT) values. It is diagnosed by determining protein level and coagulation activity (FVII:C). FVII:C measurements are expensive and time consuming.

Objectives: To analyze correlations between PT, international normalized ratio (INR), and FVII:C in pediatric patients before otolaryngology surgery and to establish alternative methods for identifying FVII deficiency.

Methods: FVII:C data were collected from 96 patients with normal aPTT and prolonged PT values during preoperative otolaryngology surgery coagulation workup between 2016 and 2020. We compared demographic and clinical parameters using Spearman correlation coefficient and receiver operating characteristic (ROC) curve analysis to determine the accuracy of PT and INR values to predict FVII deficiency.

Results: The median values of PT, INR and FVII:C were 13.5 seconds, 1.14, and 67.5%, respectively. In total, 65 participants (67.7%) displayed normal FVII:C compared to 31 (32.3%) with decreased FVII:C. A statistically significant negative correlation was observed between FVII:C and PT values and between FVII:C and INR. Despite statistically significant ROC of 0.653 for PT (P-value = 0.017, 95% confidence interval [95%CI] 0.529–0.776) and 0.669 for INR (P-value = 0.08, 95%CI 0.551–0.788), we were unable to determine an optimal cutoff point to predict FVII:C deficiency with high sensitivity and high specificity.

Conclusions: We could not identify a PT or INR threshold to best predict clinically relevant FVII:C levels. When PT is abnormal, determining FVII:C protein levels is needed for diagnosing FVII deficiency and considering surgical prophylactic treatment.

Atrial fibrillation is becoming an increasingly important problem in cardio-oncology. Specific risk factors for atrial fibrillation occurrence include type of cancer disease and anticancer drugs. Anticoagulation is often abandoned. The CHA₂DS₂-VASc and CHA₂DS₂ scores may be important not only in predicting stroke but also in mortality. The role of new direct oral anticoagulants is growing, but they need to be used in a personalized approach depending on the risk of unbeneficial interactions with cancer treatment and the risk of bleeding.

Background: Limited data exist regarding the safety of ultrasound-guided femoral nerve blockade (US-FNB) in patients with hip fractures treated with anti-Xa direct oral anticoagulants (DOAC).

Objectives: To compare the safety outcomes of US-FNB to conventional analgesia in patients with hip fractures treated with anti-Xa DOAC.

Methods: This observational exploratory prospective study included 69 patients who presented to our emergency department (ED) in 3 years with hip fracture and who were treated with apixaban or rivaroxaban. Patients received either a US-FNB (n=19) or conventional analgesics (n=50) based on their preference and, and the presence of a trained ED physician qualified in performing US-FNB. Patients were observed for major bleeding events during and 30 days after hospitalization. The degree of preoperative pain and opioid use were also observed.

Results: We found no significant difference in the number of major bleeding events between groups (47.4% vs. 54.0%, P = 0.84). Degree of pain measured 3 and 12 hours after presentation was found to be lower in the US-FNB group (median visual analog scale of pain improvement from baseline of -5 vs. -3 (P = 0.002) and -5 vs.-4 (P = 0.023), respectively. Opioid administration pre-surgery was found to be more than three times more common in the conventional analgesia group (26.3% vs.80%, P < 0.0001).

Conclusions: Regarding patients treated with Anti-Xa DOAC, US-FNB was not associated with an increase in major bleeding events compared to conventional analgesia, although it was an effective means of pain alleviation. Larger scale randomized controlled trials are required to determine long-term safety and efficacy.

Background: An association was shown between thrombocytosis and future development of several cancers.

Objectives: To investigate whether pre-treatment platelet counts correlated with clinical outcomes of patients with breast cancer.

Methods: This retrospective study included 22 patients who had been diagnosed with stage I breast cancer and were 66.8 ± 13.2 years of age. Of these, 22 with stage II were 61.6 ± 12.3 years old and 9 with stage III and IV were 64.4 ± 15.3 years old. Clinical and hematological data from the first visit to the oncology clinic were collected. The follow-up period was 12 months to 5 years.

Results: A significant difference in platelet counts was found between patients who died (187,000 ± 4000 µ/L) and those who were disease free for 5 years (248,000 ± 83,000 µ/L, P = 0.0001). A significant difference in platelet-to-lymphocyte ratio was found between patients who died and those with recurrence (192 ± 81 vs. 124 ± 71, P = 0.01). A negative correlation was found between age and lymph nodes (Ps = -0.305, P = 0.02) and staging and white blood cells count (Ps = -0.280, P = 0.04). A positive correlation was found between clinical staging and lymph nodes (Ps = 0.443, P = 0.001) and clinical staging and metastases (P = 0.308, P = 0.02).

Conclusions: Platelet counts may be a prognostic marker for breast cancer. Patients who died within 1 year had lower pre-treatment platelet count, which could represent an insidious disseminated intravascular coagulopathy cancer related consumption process.

Background: Congenital factor VII deficiency is a rare recessive autosomal bleeding disorder with a wide spectrum of clinical manifestations.

Objectives: To compare the clinical and laboratory findings in Jewish and Bedouin patients with factor VII deficiency.

Methods: The clinical and laboratory findings of patients with factor VII deficiency treated at Soroka Medical Center, a tertiary hospital in Israel, from 2005 to 2015 were analyzed regarding blood factor levels, illness severity, treatment administration, and disease outcome.

Results: Seventy-eight patients were enrolled (1:13,000 of the population in southern Israel) of whom 26 were diagnosed with severe factor VII deficiency (1:40,000). Sixty (76.9%) patients were Jewish and 18 (23.1%) were Bedouin. In univariable analysis, Bedouin patients exhibited a more severe illness, with significantly higher complication and fatality rates, and required more preventive treatment than the Jewish patients.

Conclusions: The prevalence of congenital factor VII deficiency (including severe deficiency) in the Jewish and Bedouin populations of southern Israel is higher than previously reported. The clinical spectrum of the disease was found to be more severe in the Bedouin population.

Background: Brief episodes of atrial tachycardia are a common finding in the Holter monitor recordings of elderly patients. Episodes of atrial tachycardia may convert to atrial fibrillation. Current guidelines do not recommend anticoagulant therapy in patients with atrial tachycardia and risk factors for embolism. 

Objectives: To assess the incidence of atrial tachycardia in a 24 hour Holter monitor recording of patients admitted to hospital with ischemic stroke. 

Methods: The patient cohort included two groups: 134 patients admitted with a diagnosis of ischemic stroke (the study group), and 68 consecutive patients admitted with a diagnosis of syncope (the control group). Both groups used a Holter monitor.

Results: There was no difference in the incidence of atrial tachycardia runs between the groups. Patients who suffered a stroke were more likely to be hypertensive (P < 0.05) and more likely to have a CHA2DS2-VASc score of ≥ 3 (P = 0.05).

Conclusions: Atrial tachycardia as recorded on a Holter monitor was not more prevalent in patients presenting with ischemic stroke. The occurrence of atrial tachycardia is not an indication for systemic anticoagulation. 

 

Background: The 20%–60% rate of acute anterior myocardial infarction (AAMI) patients with concomitant left ventricular thrombus (LVT) formation dropped to 10–20% when thrombolysis and primary percutaneous coronary intervention (PPCI) were introduced.

Objective: To test our hypothesis that prolonged anticoagulation post-PPCI will lower the LVT incidence even further.

Methods: Included in this study were all 296 inpatients with ST elevation AAMI who were treated with PPCI (from January 2006 to December 2009). Treatment included heparin anticoagulation (48 hours) followed by adjusted doses of low molecular weight heparin (3 more days). All patients underwent cardiac echocardiography on admission and at discharge. LVT and bleeding complications were reviewed and compared.

Results: LVT formation was present on the first echocardiogram in 6/296 patients. Another 8/289 patients displayed LVT only on their second echocardiogram (4.7%, 14/296). LVT patients had significantly lower LV ejection fractions than non-LVT patients at admission (P < 0.003) and at discharge (P < 0.001), and longer time to reperfusion (P = 0.168). All patients were epidemiologically and clinically similar. There were 6 bleeding episodes that required blood transfusion and 11 episodes of minor bleeding.

Conclusions: Five days of continuous anticoagulation therapy post-PPCI in inpatients with AAMI is associated with low LVT occurrence without remarkably increasing bleeding events.
 

Background: Atrial fibrillation (AF) is the most common arrhythmia in adults and is associated with increased mortality and morbidity.

Objectives: To characterize patients diagnosed with AF in primary care clinics in southern Israel.

Methods: We conducted a cross-sectional study in 14 primary care clinics of the largest health insurance fund in Israel, reviewing the electronic medical records of adults aged ≥ 25 years diagnosed with AF. The prevalence, evaluation, antithrombotic treatment and treatments for rate control/rhythm control were analyzed.

Results: We retrieved the records of 995 patients with a diagnosis of AF; the prevalence of AF was 1.5% (2.5% aged ≥ 45 years). The patients’ mean age was 73.5 ± 1.4 years and 55.3% were female. Vitamin K antagonist (VKA) was prescribed for 591 patients (59%), of whom 8.5% had no international normalized ratio follow-up tests for at least 3 months before our review. Among patients in the VKA treatment group the risk for thromboembolic events was considered to be high, moderate and low in 22% (n=131), 66% (n=391) and 12% (n=69), respectively. Patients with a low Congestive Hypertension Age Diabetes Stroke (CHADS2) score (odds ratio = 0.555, 95% confidence interval 0.357–0.862) and patients who did not receive VKA (OR[1] = 0.601, 95% CI[2] 0.459–0.787) received significantly less rate-control treatment. Of the patients with a low CHADS2 score (< 1) 52.7% received VKA treatment, and 39.4% with a high CHADS2 score (≥ 3) did not receive VKA. A positive correlation between anticoagulation and rate or rhythm control was found.

Conclusions: The prevalence and age distribution of AF in southern Israel are similar to findings in the western world. Many of the patients did not receive appropriate antithrombotic prophylaxis.

Background: Whereas procoagulation abnormalities in acute stress are well established, little is known about the mechanism of hypercoagulation in chronic stress, such as post-traumatic stress disorder (PTSD). This is crucial, given the fact that chronic coagulation disturbances have been associated with increased morbidity and premature mortality due to thromboembolism and cardiovascular disorders, complications recently described in PTSD patients.

Objectives: To explore the mechanisms of hypercoagulation in chronic PTSD.

Methods: Thirty patients diagnosed with chronic PTSD were enrolled and compared with a control group matched for age, gender and ethnicity. Hypercoagulation state was evaluated by levels of fibrinogen, D-dimer, prothrombin fragment F 1+2, von Willebrand factor (vWF) antigen, factor VIII activity, activated protein C resistance, ProC Global assay, and tissue factor antigen. Psychiatric evaluation was performed using the Mini-International Neuropsychiatric Interview and Clinician Administered PTSD Scale (CAPS).

Results: vWF antigen levels were significantly higher in patients with chronic PTSD compared with the controls (121.3 ± 42 vs. 99.7 ± 23, respectively, P = 0.034). Higher levels of vWF antigen and factor VIII activity were found in patients with severe chronic PTSD (CAPS > 80), compared to controls and patients with chronic PTSD and less severe symptoms (CAPS ≤ 80). However, no differences were observed in any other studied coagulation parameters between patients and controls.

Conclusions: Increased levels of vWF antigen and factor VIII activity were documented in severe chronic PTSD. These findings suggest that the higher risk of arterial and venous thromboembolic events in PTSD patients could be related to endothelial damage or endothelial activation.
 

Idiopathic pulmonary arterial hypertension (IPAH) is an isolated small-vessel disease comprising vasoconstriction, remodeling and thrombosis of small pulmonary arteries. However, there is evidence that IPAH[1] does not respect anatomic boundaries and might extend into large vessels such as large central thrombi. On the other hand, chronic thromboembolic pulmonary hypertension (CTEPH) represents a distinct category of pulmonary hypertension as it is thought to be due to an occlusion of the major pulmonary arteries following a thromboembolic event. However, it is currently evident that in most patients, there is a concomitant small-vessel disease. The involvement of both small and large vessels in both IPAH and CTEPH[2] together with a high incidence of silent thromboembolic events might create difficulties in identifying the true cause of pulmonary hypertension. An accurate diagnosis of the cause determines the management and prognosis. Patients with CTEPH can potentially be offered curative surgery in the form of pulmonary endarterectomy; however, oxygen, vasodilators, anticoagulation, and lung transplantation are more feasible options for IPAH.