Prophylactic Administration Of Heparin Research Articles

Bleeding Associated with Prophylactic Anticoagulation for Hospital Related Venous Thromboembolism Prevention: A Case Series

The use of heparin products for prophylaxis of venous thromboembolism (VTE) have decreased the prevalence of VTE in all hospitalized patients, however the possibility of bleeding from prophylactic heparin cannot be disregarded. While life-threatening bleeding is less common with prophylactic doses, it can occur in the presence of other risk factors for bleeding. We aim to describe characteristics that may increase bleeding risk from prophylactic use of heparin. We present a single-center, retrospective case series of patients who received protamine for bleeding complications from prophylactic heparin administration at our facility between 2016-2020. We assessed patient demographics, medical history, types of heparin formulations administered, and patient outcomes. We observed that all patients were female. Patients who developed bleeding events from VTE prophylaxis had at least two of these attributes; BMI <18.5 kg/m2, weight <50kg, trauma within 1-month, surgery within 1-month or were taking anti-platelet agents. We suggest that the collective presence of two or more of these characteristics should lend consideration to dose adjustment and/or closer monitoring. In the absence of rigorous research comparing alternative doses to standard doses for prophylaxis in these patients, these decisions fall largely to the discretion of individual physicians. Designing larger studies following patients over long periods of time can help conclusively identify risk factors that predispose patients to bleeding.

Six-Month Pulmonary Impairment after Severe COVID-19: A Prospective, Multicentre Follow-Up Study

Background: Long-term pulmonary sequelae following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia are not yet confirmed; however, preliminary observations suggest a possible relevant clinical, functional, and radiological impairment. Objectives: The aim of this study was to identify and characterize pulmonary sequelae caused by SARS-CoV-2 pneumonia at 6-month follow-up. Methods: In this multicentre, prospective, observational cohort study, patients hospitalized for SARS-CoV-2 pneumonia and without prior diagnosis of structural lung diseases were stratified by maximum ventilatory support (“oxygen only,” “continuous positive airway pressure,” and “invasive mechanical ventilation”) and followed up at 6 months from discharge. Pulmonary function tests and diffusion capacity for carbon monoxide (DLCO), 6-min walking test, chest X-ray, physical examination, and modified Medical Research Council (mMRC) dyspnoea score were collected. Results: Between March and June 2020, 312 patients were enrolled (83, 27% women; median interquartile range age 61.1 [53.4, 69.3] years). The parameters that showed the highest rate of impairment were DLCO and chest X-ray, in 46% and 25% of patients, respectively. However, only a minority of patients reported dyspnoea (31%), defined as mMRC ≥1, or showed restrictive ventilatory defects (9%). In the logistic regression model, having asthma as a comorbidity was associated with DLCO impairment at follow-up, while prophylactic heparin administration during hospitalization appeared as a protective factor. The need for invasive ventilatory support during hospitalization was associated with chest imaging abnormalities. Conclusions: DLCO and radiological assessment appear to be the most sensitive tools to monitor patients with the coronavirus disease 2019 (COVID-19) during follow-up. Future studies with longer follow-up are warranted to better understand pulmonary sequelae.

Anti-SS-A (Ro) antibody is positively associated with steroid-induced psychiatric events in systemic lupus erythematosus patients

Forty-five systemic lupus erythematosus (SLE) patients who had steroid at a prednisolone dose of 0.8 mg/kg/day or more were retrospectively studied for psychiatric events that developed after the therapy. Simple insomnia was excluded. Their age, sex, dose, and duration of steroid, autoantibodies, and prophylactic heparin use were examined. Seventeen patients (female/male: 16/1, 36.7 ± 10.7 years old) developed psychiatric events 18.2 ± 10.2 days after steroid start, whereas 28 patients (27/1, 37.9 ± 13.1) did not. Anti-SS-A (Ro) antibody was more prevalent in patients with the events (15/17 vs. 14/28, p = 0.009). When heparin was administered concurrently with steroid, psychiatric events developed less frequently either in all of the patients (2/17 vs. 11/28, p = 0.048) or in patients positive for the anti-SS-A antibody (2/15 vs. 7/14, p = 0.041). SLE patients positive for the anti-SS-A (Ro) antibody would much more likely develop psychiatric events after a substantial-dose steroid therapy, and a concurrent prophylactic heparin administration might reduce the risk.

Thrombophilia and its impact on pregnancy

In recent years thrombophilia has gained much attention as a risk factor for pregnancy complications. Whereas there is an established correlation between antiphospholipid antibodies and pregnancy loss, data for other risk factors of thrombosis are less well established. Data suggest associations with antithrombin deficiency, hyperhomocysteinemia and also with factor V Leiden, prothrombin G20210A variation and protein S-deficiency. The association of thrombophilia with pre-eclampsia is still under discussion. A limited number of prospective studies did not reveal an increased risk for pregnancy complications in unselected women with thrombosis risk factors. In a single study low molecular weight heparin seemed to have a positive effect on pregnancy outcome after previous single or recurrent abortions. Experience in prevention of pre-eclampsia by administration of prophylactic heparin is very limited. Data on pregnancy complications in women with known heritable thrombophilia or a history of thrombosis are inconsistent as well. These women usually have a favourable pregnancy outcome. In conclusion, thrombophilia screening might be justified in women with pregnancy loss, and treatment with low molecular weight heparin might be considered for those with pregnancy loss and thrombophilia. Further prospective studies and controlled interventional trials are urgently needed.

Thrombophilia and its impact on pregnancy

In recent years thrombophilia has gained much attention as a risk factor for pregnancy complications. Whereas there is an established correlation between antiphospholipid-antibodies and pregnancy loss, data for other risk factors of thrombosis are less well established. Data suggest associations with antithrombin deficiency, hyperhomocysteinemia and also with factor V Leiden, prothrombin G20210A variation and protein S-deficiency. The association of thrombophilia with pre-eclampsia is still under discussion. A limited number of prospective studies did not reveal an increased risk for pregnancy complications in unselected women with thrombosis risk factors. In a single study low molecular weight heparin seemed to have a positive effect on pregnancy outcome after previous single or recurrent abortions. Experience in prevention of pre-eclampsia by administration of prophylactic heparin is very limited. Data on pregnancy complications in women with known heritable thrombophilia or a history of thrombosis are inconsistent as well. These women usually have a favourable pregnancy outcome. Thrombophilia screening might be justified in women with pregnancy loss. Treatment with low molecular weight heparin might be considered for those with pregnancy loss and thrombophilia. Further prospective studies and controlled interventional trials are urgently needed.

International multi-centre study of incidence and risk factors of symptomatic deep venous thrombosis (DVT) and or pulmonary embolism (PE) in prostate cancer patients undergoing laparoscopic radical prostatectomy (LRP)

8555 Background: There is no data regarding the incidence and variables associated with symptomatic DVT and or PE in patients undergoing LRP. Our aim was to evaluate the multi-centric incidence and risk factors for perioperative symptomatic DVT and PE after LRP. Methods: Patients with symptomatic DVT and or PE occurring within 2 months of surgery since start of the respective institutional LRP experience were included. Eight academic centers from both the United States and Europe participated. Diagnoses were made by Doppler ultrasound for DVT; and lung ventilation/perfusion scan and or chest computed tomography for PE. Associations between variables and DVT and/or PE were evaluated using Fisher’s exact test for categorical predictors and logistic regression for continuous predictors. Results: Patient reoperation (p value) (<0.001), tobacco exposure (0.02), prior DVT (0.007), larger prostate size (0.02) and length of hospital stay (0.009) were significantly associated with higher risk of symptomatic DVT/PE. The nonuse of perioperative heparin was not a risk factor (1), as well as neoadjuvant therapy (1), perioperative transfusion (0.1), body mass index (0.9), surgical technique (0.3), operating time (0.2) and pathologic stage (0.5). There were no related deaths. Patients receiving preoperative heparin had significantly higher mean operative blood loss, 480cc vs 332cc (<0.001) However, this did not translate into longer hospital stay (0.07); higher transfusion rates (0.09) or reoperation rates (0.3). The estimated cost of heparin prophylaxis in these patients exceeded $2.5 million. Conclusion: The incidence of symptomatic DVT or PE was similar despite different prophylactic regimens. Our data does not support the administration of prophylactic heparin in LRP to low risk patients (no prior DVT, no tobacco exposure, no prostate enlargement and or no anticipation of prolonged hospital stay). [Table: see text] No significant financial relationships to disclose.

Effects of heparin in experimental models of acute pancreatitis and post-ERCP pancreatitis

Background Acute pancreatitis (AP) is a complication of diagnostic or therapeutic endoscopic retrograde cholangiopancreatography (ERCP). In a recent clinical trial, a decreased rate of post-ERCP pancreatitis was shown after prophylactic heparin treatment. The aim of this study was to evaluate the effects of prophylactic heparin application in various experimental models of AP and pancreatic duct obstruction and to assess the underlying mechanisms. Methods In various experimental models, pancreatic injury of graded severity was induced in Wistar rats: (1) mild pancreatitis by IV cerulein infusion over 6 hours; (2) severe pancreatitis by infusion of glycodeoxycholic acid into the pancreatic duct plus IV cerulein application over 6 hours. The clinical ERCP situation was imitated in groups (3) obstruction of the pancreatic duct and (4) infusion of contrast medium into the pancreatic duct plus obstruction. In every group the animals received either no heparin (n = six per group) or continuous IV heparin (n = six per group) starting before pancreatic injury. Histologic changes, amylase, and lipase in plasma were evaluated 12 hours after induction of pancreatic injury. Additional animals were treated to investigate pancreatic microcirculation by intravital microscopy (n = six per group). Results In groups 1, 3, and 4 (mild AP/duct obstruction/duct obstruction plus contrast medium), IV heparin-treated animals showed reduced edema, inflammation, and peak amylase values compared with the corresponding non-heparin-treated animals (P<.05). Moreover, mean erythrocyte velocity was significantly higher and leukocyte-endothelium interaction was reduced in these groups after prophylactic administration of heparin. In contrast, group 2 (severe AP) did not show any difference between control animals and animals that received heparin as assessed by histology and intravital microscopy. Conclusions Prophylactic systemic application of heparin provides a protective effect in mild AP and in experimental post-ERCP pancreatitis. The mechanism of the protective effects of heparin seems to be the reduction of leukocyte-endothelium interaction and the normalization of pancreatic microcirculation.

The Risk of Thromboembolism in Asymptomatic Patients with Protein C and Protein S Deficiency: A Prospective Cohort Study

Prospective studies on the incidence of thrombosis in asymptomatic individuals with hereditary protein C- or protein S deficiency have not been performed so far. We have carried out a prospective cohort study in 44 asymptomatic protein C- and protein S deficient subjects and in 49 asymptomatic non-deficient relatives (age at study entry > 14 years) of symptomatic deficient patients. 20 asymptomatic protein C deficient (median age 20 years) and 24 asymptomatic protein S deficient patients (median age 21.5 years) were prospectively followed and compared with 20 asymptomatic non-deficient relatives (median age 25 years) of protein C- and 29 (median age 27 years) of protein S deficient patients. The total observation period was 118.8 patient years for protein C deficient and 92.8 for protein S deficient patients. Patients were not on anticoagulants except for short duration in case of high risk situations. Eight thromboembolic events (1 pulmonary embolism, 1 deep vein thrombosis + pulmonary embolism, 3 deep vein thrombosis, 1 caval vein thrombosis and 2 superficial vein thrombosis) occurred in 6 deficient patients. The incidence of thromboembolism was 2.5% per patient year for protein C deficient and 3.5% per patient year for protein S deficient patients. 4 events occurred spontaneously, in 2 patients thromboembolic events were triggered by high risk situations (caesarean section, minor trauma). In the controls no thromboembolic events occurred. The probability for thromboembolism was significantly higher in protein C and protein S deficient patients compared to the control group (Wilcoxon test, p = 0.002, log rank test, p = 0.001). One major and 5 minor uneventful surgeries were carried out in the deficient patients using heparin prophylaxis. 1/8 pregnancies was complicated by superficial vein thrombosis during the second trimester despite prophylactic heparin administration. The same pregnancy was complicated by pulmonary embolism 5 weeks after delivery after discontinuation of heparin. Asymptomatic deficient relatives of symptomatic patients with protein C or protein S deficiency are at an increased risk of thrombosis compared to nondeficient individuals. Prophylactic treatment seems to be highly effective in high risk situations.

Heparin treatment in thrombin-induced disseminated intravascular coagulation in the baboon

We postulated that low-dose heparin (10 IU/kg.hr) administered as a continuous iv infusion may prevent or ameliorate the induction of thrombin-induced disseminated intravascular coagulation in baboons under general anesthesia. In a nonrandomized experiment lasting 8 hrs, animals were divided into three groups: 11 received thrombin only (group A); ten were pretreated with heparin before thrombin administration (group B); and 15 received heparin 2 hrs after disseminated intravascular coagulation was induced with thrombin (group C). All animals were monitored hemodynamically and coagulation tests were performed hourly. Tests included the following: one-stage prothrombin ratio; activated partial thromboplastin time; fibrinogen and fibrin degradation products; thrombin time; plasma fibrinogen level; antithrombin III and activated clotting time. After the acute phase of the experiment, the animals were observed for 6 days and a postmortem examination was performed on a survivor of each group. Six (55%) group A animals died within 6 days, while there were no deaths in group B and one animal (7%) died in group C. In group C, the administration of heparin could not normalize the clotting profile, but the mortality rate was significantly less than in group A. The prophylactic administration of heparin in group B prevented the induction of disseminated intravascular coagulation. The postmortem findings were of interest, but no statistically valid conclusions could be made, as only one autopsy was done for each group. However, the results suggest that heparin pretreatment may protect against lung edema and liver necrosis. The results suggest that heparin, in a dose of 10 IU/kg.hr iv, could possibly be safely used in patients at high risk of developing disseminated intravascular coagulation and in those patients with established disseminated intravascular coagulation.

Low-dose heparin. A cause of hematoma of rectus abdominis

Although hematomas of the rectus abdominis muscle are commonly reported complications of systemic anticoagulation treatment, they are a rare complication of prophylactic administration of low-dose heparin. The occurrence of a massive hematoma of the rectus sheath is reported in a woman with chronic obstructive pulmonary disease and acute respiratory failure who was receiving low doses of heparin for the prevention of deep venous thrombosis. Three other cases of hematoma of the rectus sheath resulting from prophylactic use of heparin are reviewed. The development of hematoma in these patients may have resulted from intramuscular abdominal injection of heparin and from strain of the rectus abdominis muscle caused by coughing. When prophylactic administration of heparin is necessary in patients with a tendency to paroxysmal cough, subcutaneous injections of heparin in the thigh may be preferable to subcutaneous injections in the abdomen.

Management of acute occlusion after percutaneous transluminal coronary angioplasty.

Acute coronary occlusion is a not infrequent complication of angioplasty. When it persists, it commonly leads to myocardial infarction, and sometimes to death. Ideally, it should be prevented by careful attention to technical predisposing factors and the routine prophylactic administration of heparin and aspirin. There are a number of strategies for managing the problem when it does occur; these frequently include re-angioplasty with standard or perfusion balloon catheters and the use of stents or atherectomy. However, if prompt reopening is not possible, then immediate coronary artery bypass grafting may be the wisest choice.

Sudden Hearing Loss Due to Diving and Its Prevention with Heparin

Vascular embolic and thrombotic problems postulated to be the cause of inner ear sudden deafness have been reported with decompression sickness also. Decompression sickness has been found to lead to cochlear potential loss in the guinea pig, and these losses are minimized by the prophylactic administration of heparin. Preliminary results show that inner ear hemorrhage may be associated with diving deafness, but plasma protein leakage into the perilymph of the ear may precede the hemorrhage. Inner ear hemorrhage in diving deafness seems to be restricted to the microcirculation. Until we gain a better understanding of the pathophysiology of diving induced deafness, it would be premature to consider agents such as heparin for the treatment of the problem in man.

PREVENTION OF FATAL POSTOPERATIVE THROMBOEMBOLISM BY HEPARIN PROPHYLAXIS

In a continuing study, begun in 1960, of perioperative administration of heparin in small doses, there has been 1 confirmed death from thromboembolism, and no instance of myocardial infarction, in 750 predominantly severe-risk cases. Over the same period, among 18,729 average-risk cases in which operation was undertaken without prophylactic administration of heparin, deaths from thromboembolism amounted to 1 in 90 cases or, including myocardial infarction, 1 in 70 cases. In the treated group the dosage of heparin was controlled, by means of a modified Dale and Laidlaw coagulometer, to maintain the coagulation-time at a normal level. In each of the only 2 instances where excessive bleeding at operation was attributed to heparin, this complication was traced to inadvertently incorrect administration of the anticoagulant.

PREVENTION OF SUDDEN CARDIOPULMONARY ARREST IN THE PERIOPERATIVE PERIOD WITH PROPHYLACTIC HEPARIN

The observation that most cases of fatal cardiopulmonary arrest in the perioperative period showed necropsy evidence of thromboembolism suggested that an anticoagulant given prophylactically might reduce the incidence of this serious hazard in the perioperative period. 565 patients, at risk on account of age or previous history and down for a major surgical procedure, were given 10,000 units of heparin subcutaneously at midnight before the morning of the operation. The object was to attain normal coagulation-times (controlled by a modified Dale and Laidlaw method). Of this series, 2 patients died in cardiopulmonary arrest, but in neither was there any necropsy evidence of thromboembolism. The experience suggests that thrombotic cardiopulmonary arrest in the perioperative period can be prevented by the prophylactic administration of heparin.