Not Just Anticoagulation-New and Old Applications of Heparin.

In recent decades, heparin, as the most important anticoagulant drug, has been widely used in clinical settings to prevent and treat thrombosis in a variety of diseases. However, with in-depth research, the therapeutic potential of heparin is being explored beyond anticoagulation. To date, heparin and its derivatives have been tested in the protection against and repair of inflammatory, antitumor, and cardiovascular diseases. It has also been explored as an antiangiogenic, preventive, and antiviral agent for atherosclerosis. This review focused on the new and old applications of heparin and discussed the potential mechanisms explaining the biological diversity of heparin.

Cardiovascular risk in COVID-19 infection.

A few months ago a new coronavirus was identified in Cina officially named by the WHO as COVID-19. The thousands of patients who died showed pneumonia and alveolar damage, but actually, according to several authors in addition to the acute respiratory distress syndrome the virus can give rise to multiorgan failure. In fact, many people died equally despite being intubated and treated for respiratory failure. In this review, we especially wanted to describe the virus effects on the cardiovascular system, probably the leading cause of death of thousands of deceased patients. Therefore, mortality is indirectly induced by the virus through vascular inflammation and cardiovascular damage and patients with severe COVID-19 infection showed significantly increased levels of cardiac troponin I and inflammatory cytokines. The main activation of the signal pathways for the production of inflammatory cytokines are the toll-like receptors that recognize the presence of viral nucleic acids and the ACE-2 receptors, that the virus uses to infect the cells. The binding to ACE-2 also allows to promote high levels of angiotensin II by promoting high levels of blood pressure. High levels of IL-6, IL-1B and IL-8 have been associated with plaque instability and increased thrombotic risk. Furthermore IL-6 is involved in the stimulation of matrix-degrading enzymes such as matrix metalloproteinases, and may contribute to the development of acute coronary syndrome. In addition, TNF-α, IL-1 and IL-6 present in patients with severe COVID-19 are associated with coagulation activation and thrombin generation resulting in disseminated intravascular coagulation or thrombotic microangiopathy. Considering these pathological effects of the virus, anti-inflammatory and anticoagulant treatments are to be considered to avoid cardiovascular events. In this regard, heparin, in addition to its anticoagulant characteristics, has been shown to have good control over inflammation and to be a good anti-viral drug.

Accuracy, reproducibility and costs of different laboratory assays for the monitoring of unfractionated heparin in clinical practice: a prospective evaluation study and survey among Swiss institutions.

OBJECTIVES: To investigate the accuracy, reproducibility and costs of different laboratory assays for the monitoring of unfractionated heparin (UFH) in clinical practice and to study test utilisation in Switzerland. DESIGN: Prospective evaluation study and survey among Swiss hospitals and laboratories. SETTING: Secondary care hospital in rural Switzerland (evaluation study); all Swiss hospitals and laboratories (survey). PARTICIPANTS: All consecutive patients, monitored for treatment with UFH during two time periods, were included (May to July 2014 and January to February 2015; n=254). OUTCOME MEASURES: Results of activated partial thromboplastin time (aPTT), thrombin time (TT), prothrombinase-induced clotting time (PiCT) and anti-Xa activity with respect to UFH concentration RESULTS: Spearman's correlation coefficient (rs) with regard to anti-Xa activity was 0.68 (95% CI 0.60 to 0.75) for aPTT, 0.79 (0.69 to 0.86) for TT and 0.94 (0.93 to 0.95) for PiCT. The correlation (rs) between anti-Xa activity and heparin concentration as determined by spiking plasma samples was 1.0 (1.0 to 1.0). The coefficient of variation was at most 5% for PiCT and anti-Xa activity (within-run as well as day-to-day variability). The total costs per test in Swiss Francs (SFr) were SFr23.40 for aPTT, SFr33.30 for TT, SFr15.70 for PiCT and SFr24.15 for anti-Xa activity. The various tests were employed in Swiss institutions with the following frequencies: aPTT 53.2%, TT 21.6%, anti-Xa activity 7.2%, PiCT 1.4%; 16.6% of hospitals performed more than one test. CONCLUSIONS: The accuracy and reproducibility of PiCT and anti-Xa activity for monitoring of UFH was superior, and analytical costs were equivalent to or lower than aPTT and TT.

Outcome of Sub-Massive Pulmonary Thromboemboli in Patients Who Received Thrombolytic and or Non-Thrombolytic Therapy.

BACKGROUND: Thrombolytic therapy in patients with sub-massive pulmonary embolism (SMPTE) needs further assessment. OBJECTIVES: The current study aimed to assess a potential benefit of thrombolytic and non-thrombolytic therapy in patients with SMPTE. PATIENTS AND METHODS: One hundred-nineteen patients were enrolled with SMPTE from 2006 to 2010 in the tertiary care center of Rajaie medical and research center. The patients who had pulmonary thromboemboli (PTE) and received thrombolytic plus heparin therapy and or non-thrombolytic (unfractionated heparin alone) were evaluated for hemodynamic changes (blood pressure, pulse rate, pulmonary artery systolic pressure, right ventricular failure and right ventricle enlargement), before and after 48 hours of treatment. The mortality rate was also assessed. RESULTS: Forty-five percent of the patients with SMPTE received thrombolytic therapy (streptokinase) and 55% of SMPTE patients received non-thrombolytic therapy (unfractionated heparin). Pulse rate, pulmonary arterial pressure and tricuspid regurgitation gradient in patients receiving thrombolytic therapy reduced significantly (P = 0.001, P = 0.01 and P = 0.001, respectively). There was no significant difference before and after treatment regarding systolic blood pressure (P = 0.4), diastolic blood pressure (DBP) (P = 0.5), systolic arterial pressure (SPAP) (P = 0.1), Right ventricular (RV) function (P = 0.1) and RV size (P = 0.1). In patients who received a non-thrombolytic therapy, there were no significant differences between the groups regarding SBP (P = 0. 2), DBP ( P= 0. 4) and PR (P = 0. 1), SPAP (P = 0.6), TRG (P = 0.4), RV function (P = 0.4) and RV size (P = 0.2) before and after treatment. There were no significant differences between the groups according to mortality rate. CONCLUSIONS: Thrombolytic therapy lead to earlier relief of hemodynamic condition in comparison to non-thrombolytic therapy but no changes were observed in mortality rate.

[Clinical and therapeutic aspects of post-partum cerebral thrombophlebites]. / Les aspects cliniques et thérapeutiques des thrombophlébites cérébrales du post-partum.

Cerebral thrombophlebites are rare but life-threatening conditions (1/5000 births). Pregnancy and postpartum are predisposing factors: clinical presentation vary and may be misleading, dominated by headaches, convulsions and neurological deficits but showing no specific features. Physical examination often generates informations unavailable and misleading because cerebral thrombophlebites share symptoms with other affections. A definitive diagnosis can be made only neuroradiologically. Brain MRI is currently the reference method; it allows visualization of the venous thrombus and its evolution. The treatment of cerebral thrombophlebites is essentially medical based on anticoagulant drugs. We here report four cases with post partum cerebral thrombophlebites. The aim of our study and review of the literature is to highlight the importance of early diagnosis and adequate therapy.

Successful management of neonatal renal venous thrombosis.

Renal vein thrombosis is the most common vascular condition involving the newborn kidney and it can result in severe renal damage. We report a newborn with renal vein thrombosis treated with continuous infusion of unfractionated heparin who had normal total renal function after 3 years of follow up, despite reduction of the functional contribution of the affected kidney.

Underestimation of unfractionated heparin therapy assessment due to platelet activation when using partial-draw (pediatric) citrate collection tubes.

The "so-called" pediatric tubes are often used when collecting smaller blood volume is necessary, particularly in pediatric patients or in case of difficult/recurrent sampling. The aim of this multicenter study was to compare coagulation test results evaluated in evacuated polymer tubes containing 0.109 M citrate (1 vol./9 vol.) specifically designed to allow either a partial (2.0 mL,"pediatric") or a total (3.5 mL) filling. No significantly relevant discrepancy was found between routine coagulation test results in both tubes collected from untreated patients and from patients on vitamin K antagonist or low molecular weight heparin. In contrast, aPTT was significantly shorter and anti-FXa activity was significantly lower in partial-draw than in full-draw tubes collected from 46 patients receiving unfractionated heparin (UFH). This discrepancy was likely related to increased platelet activation in partial-draw tubes, as suggested by higher platelet factor 4 plasma concentrations and platelet P-Selectin expression in partial-draw than in full-draw citrate tubes. To confirm this hypothesis, we then evaluated partial-draw tubes containing CTAD, a mixture of anticoagulant and antiplatelet agents. In 25 patients on UFH, aPTT and anti-FXa activity were not significantly different in partial-draw CTAD tubes and in full-draw citrate tubes. In conclusion, despite increased platelet activation, samples collected into partial-draw citrate tubes allow accurate routine coagulation testing in all patients but those requiring UFH assessment, in which their use could lead to significant underestimation of anticoagulation. In such cases, partial-draw tubes containing CTAD could be validly used to monitor heparin therapy as well as to perform routine coagulation testing.

Lacunar infarction with oral contraceptives: An unusual case report.

Combined oral contraceptives are one of the risk factor for stroke in women. We report a case of an arterial ischemic stroke due to lacunar infarction in a 35-year-old previously healthy female patient induced after 3 years on Sukhi an oral contraceptive after two times artificial abortions. A brain MRI finding was suggestive of lacunar infarction. Her symptoms improved after stopping the oral contraceptive and putting her on I.V heparin therapy.

The Management of Heparin-induced Thrombocytopenia with Thrombosis after Open Heart Surgery: A Case Report / 대한구급학회지

Heparin-induced thrombocytopenia (HIT) is a prothrombotic, immune-mediated adverse reaction to heparin therapy. It is caused by antibodies binding to a complex of heparin and platelet factor 4, and this leads to platelet activation, excessive thrombin generation and often thrombosis. HIT with thrombosis (HITT) can lead to limb amputation, stroke, myocardial infarction and death. We report here on a case of a HITT patient who was successfully managed with argatroban therapy. Further knowledge is need about the ideal medical management for HITT.