Low-dose Subcutaneous Heparin Research Articles

Equivalent VTE rates after total joint arthroplasty using thromboprophylaxis with aspirin versus potent anticoagulants: retrospective analysis of 4562 cases across a diverse healthcare system

BackgroundGuidelines support aspirin thromboprophylaxis for primary total hip and knee arthroplasty (THA and TKA) but supporting evidence has come from high volume centers and the practice remains controversial.MethodsWe studied 4562 Medicare patients who underwent elective primary THA (1736, 38.1%) or TKA (2826, 61.9%) at 9 diverse hospitals. Thirty-day claims data were combined with data from the health system’s electronic medical records to compare rates of venous thromboembolism (VTE) between patients who received prophylaxis with: (1) aspirin alone (47.3%), (2) a single, potent anticoagulant (29%), (3) antiplatelet agents other than aspirin or multiple anticoagulants (21.5%), or (4) low-dose subcutaneous unfractionated heparin or no anticoagulation (2.2%). Sub-analyses separately evaluating THA, TKA and cases from lower volume hospitals (n = 975) were performed.ResultsThe 30-day VTE incidence was 0.6% (29/4562). VTE rates were equal in patients receiving aspirin and those receiving a single potent anticoagulant (0.5% in both groups). Patients with VTE were significantly older than patients without VTE (mean 76.5 vs. 73.1 years, P = 0.04). VTE rate did not associate with sex or hospital case volume. On bivariate analysis considering age, aspirin did not associate with greater VTE risk compared to a single potent anticoagulant (OR = 2.1, CI = 0.7–6.3) with the numbers available. Odds of VTE were increased with use of subcutaneous heparin or no anticoagulant (OR = 6.4, CI = 1.2–35.6) and with multiple anticoagulants (OR = 3.6, CI = 1.1–11.2). THA and TKA demonstrated similar rates of VTE (0.5% vs. 0.7%, respectively, P = 0.43). Of 975 cases done at lower volume hospitals, 387 received aspirin, none of whom developed VTE.ConclusionsThis study provides further support for aspirin as an effective form of pharmacological VTE prophylaxis after total joint arthroplasty in the setting of a multi-modal regimen using 30-day outcomes. VTE occurred in 0.7% of primary joint arthroplasties. Aspirin prophylaxis did not associate with greater VTE risk compared to potent anticoagulants in the total population or at lower volume hospitals.

Stroke and Thromboprophylaxis in the Era of COVID-19

Stroke and Thromboprophylaxis in the Era of COVID-19

Heparin for prophylaxis of venous thromboembolism in intracerebral haemorrhage

ObjectiveTo determine the occurrence of intracranial haemorrhagic complications (IHC) on heparin prophylaxis (low-dose subcutaneous heparin, LDSH) in primary spontaneous intracerebral haemorrhage (ICH) (not oral anticoagulation-associated ICH, non-OAC-ICH), vitamin K antagonist...

Abstract WP448: Safety of Heparin for Prophylaxis of Venous Thromboembolism in Oral Anticoagulation-Associated Intracerebral Hemorrhage

Introduction: Patients with intracerebral hemorrhage (ICH) have a high risk of venous thromboembolism (VTE). Next to intermittent pneumatic compressions low-dose subcutaneous heparins represent the most intuitive treatment for VTE prophylaxis. However, in the specific setting of ICH their safety remains to be verified as randomized controlled trials are missing. The present study pooled individual data of patients with spontaneous primary ICH and OAC-ICH to explore the incidence of hemorrhagic complications during hospital stay among subgroups treated with heparins for VTE prophylaxis. Methods: We integrated both parts of the RETRACE-program (part-1: 2006-2010; part-2:2011-2015) and the single-center UKER-ICH registry (2006-2015). Including all patients receiving low-dose subcutaneous heparin for VTE prevention we pooled individual patient data of 1702 vitamin-K antagonist-(VKA) or non-VKA oral anticoagulants(NOAC)-related ICH patients treated at 22 tertiary-care centers across Germany and of 1022 primary spontaneous ICH patients from UKER. We defined intracranial hemorrhagic complications (IHC) during hospital stay as primary safety outcome measure. Secondary outcomes included mortality and functional outcome (modified Rankin Scale, mRS) at 3 months of patients with and without IHC. Results: IHC occurred in 1.7%(42/2416) of ICH patients. There were no differences in crude incidence rates among patients with VKA-ICH, NOAC-ICH and non-OAC-ICH (Log rank p=0.645; Breslow p=0.753; VKA-ICH: 27/1406[1.9%], NOAC-ICH 1/130[0.8%], non-OAC-ICH 14/880[1.6%];p=0.577). Detailed analysis according to days spent on heparin prophylaxis revealed no differences in rates of IHC per 1000 patient days (VKA-ICH: 1.49[1.00-2.14], NOAC-ICH 0.63[0.03-3.13], non-OAC-ICH 1.45[0.82-2.37]; p=0.687). Secondary outcomes showed differences in functional outcome (mRS=4-6: IHC: 29/37[78.4%] vs no-IHC: 1213/2048[59.2%];p=0.019) and mortality (IHC: 14/37[37.8%] vs no-IHC: 485/2048[23.7%];p=0.045) in disfavor of IHC-patients. Conclusions: Heparin administration for VTE prophylaxis in ICH patients appears to be safe without differently increased risks of IHC among non-OAC-ICH, VKA-ICH and NOAC-ICH.

Validation of the Caprini risk assessment model for venous thromboembolism in high-risk surgical patients in the background of standard prophylaxis

We used the Caprini venous thromboembolism risk assessment score to prospectively evaluate if there was a correlation between the Caprini scores and the incidence of postoperative deep vein thrombosis (DVT) in high-risk surgical patients. A second objective was to determine whether patients at extremely high risk need a more effective prophylactic regimen. This prospective multicenter observational study involved 140 high-risk patients who underwent abdominal (48%) or cranial and/or spinal (52%) surgery. All patients were assessed using the Caprini model and had a mean score of 9.5 ± 2.7 (range, 5-15). Our standard prophylaxis for venous thromboembolism consisted of above-knee graduated compression stockings with 18 to 21 mm Hg pressure and subcutaneous low-dose unfractionated heparin three times per day, starting on the first or second through the fifth postoperative day depending on the risk of bleeding. We performed a duplex ultrasound examination at baseline during the first 12 to 24 hours after surgery and then every 3 to 5 days until discharge to assess the lower limb venous system up to the inferior vena cava. The end point of the study was ultrasound verification of fresh DVT or pulmonary embolism (PE). Verification of PE was made in all cases of DVT using echocardiography, lung scintigraphy, combined single-photon emission computed tomography and X-ray computed tomography, or autopsy. Fresh postoperative DVT was found in 39 patients (28%). The incidence of DVT was 2% in patients with a Caprini score of 5 to 8, 26% in patients with scores of 9 to 11, and 65% in patients with scores of 12 to 15 (P for trend < .01). The risk for DVT was increased 18.7-fold for patients with scores of 9 to 11 and 98.4-fold for scores of 12 to 15 compared with patients with scores of 5 to 8. The area under the receiver operating characteristic curve was 0.87 (95% confidence interval, 0.81-0.94) and a Caprini score of 11 was the cutoff point that provided the highest sensitivity combined with highest specificity. In the 77 patients with a score of <11, DVT occurred in 2 patients (3%). In contrast, in the 63 patients with a score of ≥ 11, DVT occurred in 37 patients (59%; P < .01). PE was found in 13 patients (9%) and confirmed with autopsy. In all cases, verified fresh DVT was the source of embolism. There was a significant correlation between Caprini scores and the incidence of postoperative DVT in high-risk surgical patients. A Caprini score of ≥ 11 can identify a subgroup of patients at extremely high risk. These patients need a more effective prophylactic regimen.

Postoperative prophylaxis of venous thromboembolism (VTE) in patients undergoing high ligation and stripping of the great saphenous vein (GSV).

To analyze the necessity of venous thromboembolism (VTE) prophylaxis for patients undergoing high ligation and stripping of the great saphenous vein (GSV) and to estimate the efficacy and safety of different anticoagulant protocols in a single-center randomized controlled trial with large sample size. A total of 2196 patients undergoing high ligation and stripping of the GSV were randomized to one of the following postoperative VTE prophylaxis protocols: group A, no VTE prophylaxis (n=542); group B, subcutaneous low-dose unfractionated heparin (LDUH) hypodermic injection, 125 U/kg per day in three divided doses (n=531); group C, low-molecular-weight heparin (LMWH) 6000 IU once a day (n=573); and group D, LMWH 4000 IU twice daily (n=550). Groups were compared for the incidence of VTE and major hemorrhage within 1 month following surgery. Varicose vein severity was classified by CEAP (Clinical, Etiologic, Anatomic, Pathophysiologic elements) score. The clinical characteristics of the patients were equally matched between groups. Postoperative deep vein thrombosis (DVT) and pulmonary embolism (PE) were significantly higher in group A (DVT 5.17%, PE 1.48%) compared to groups B (0.56%, 0%), C (0.35%, 0%) and D (0.36%, 0%) (p<0.01). The incidence of VTE did not differ between the three active chemoprophylaxis arms. Hemorrhagic complications were low for each group but higher in group B (0.75%) compared to the other groups (group A 0.18%; group C 0.17%; group D 0.18%, p<0.01). Hemorrhagic complications did not differ amongst groups A, C and D. In conclusion, postoperative VTE chemoprophylaxis following high ligation and GSV stripping effectively reduces the venous thrombosis complications of this procedure. Of the three active strategies tested, no difference in efficacy was noted; however, thrice daily LDUH did increase bleeding complications.

Life-Threatening Intracranial Hemorrhage With Unexpectedly High Prothrombin Time Following Venous Thromboembolism Prophylaxis

Effective thromboprophylaxis with low-dose subcutaneous heparin has been shown to reduce morbidity and mortality. Low-dose prophylactic heparin usually has very low bleeding risk and therefore, prothrombin time (PTT) monitoring or dose adjustment according to age, weight and renal function is not recommended. Life-threatening hemorrhage and markedly elevated PTT with prophylactic heparin is a very rare complication. An 86-year-old woman was admitted with urinary tract infection (UTI) and started on 5,000 U subcutaneous heparin three times a day. Patient condition improved but on day 3, she developed sudden onset of headache, confusion and drowsiness. CT of head showed massive intracranial bleed with midline shift. Craniotomy was done and hematoma was evacuated. PT/INR was normal but PTT was significantly prolonged. Rest of laboratory investigations were inconclusive which ruled out other important causes of elevated PTT and bleeding. Patient was given protamine sulphate and transfused fresh frozen plasma, packed red blood cells and platelets. Patient condition deteriorated and family decided to withdraw life support. Venous thromboembolism (VTE) prophylaxis may be complicated by hemorrhage especially in high risk patients. Heparin should be used cautiously and its effect should be monitored in such patients. Though low-dose unfractioned heparin thrice daily has been found to be superior to twice daily heparin in preventing thromboembolism, bleeding risk is higher. J Med Cases. 2015;6(7):313-317 doi: http://dx.doi.org/10.14740/jmc2193w

Thromboelastography: a more accurate assessment of global hemostasis

A 47-year-old male with acute myeloid leukemia underwent resection of a paraspinous mass. Preoperative laboratory study results were as follows: white blood cell count, 2.6 × 10 9 /L; hematocrit (Hct), 29%; platelet (PLT) count, 878 × 10 9 /L; prothrombin time, 17.2 seconds (normal, 11.9-14.4 sec); and partial thromboplastin time, 41 seconds (normal, 22-37 sec). Intraoperatively, hemostasis was difficult to achieve. Two units of plasma and one plateletpheresis were transfused. Postoperatively, incisional bleeding continued and Hct decreased to 24%. Bleeding in the setting of thrombocytosis (921 × 10 9 /L), minimally prolonged prothrombin time (16.6 sec), and mildly elevated fibrinogen concentration (420 mg/dL) prompted a transfusion medicine consultation. To assess the coagulation system, thromboelastograph (TEG 5000, Haemonetics, Braintree, MA) was obtained. TEG monitors the mechanical properties of the developing clot and subsequent lysis. Movement of an immersed transducer transmits a signal that generates a hemostasis profile. Initial TEG showed normal thrombin generation (R), but clot lysis indices (LY30 = 9.5% and CI > 1) suggested early secondary fibrinolysis, commonly seen in early disseminated intravascular coagulation (DIC). To prevent development of overt DIC, treatment with low-dose subcutaneous heparin was recommended. Four hours after heparin administration, repeat TEG showed LY30 normalized to 0%, suggesting cessation of the fibrinolytic phase of DIC. However, elevated angle and MA/G indicated higher fibrin(ogen) stabilization and PLT function, suggesting hypercoagulability. The patient received subcutaneous heparin every 12 hours for 48 hours. His bleeding resolved and he was discharged on Postoperative Day 4. This case demonstrates the clinical utility of thromboelastography. Routine laboratory testing did not suggest DIC, and transfusion of plasma and PLTs did not lead to clinical improvement; TEG evaluation allowed a more accurate assessment of all phases of coagulation, which revealed incipient DIC. As a result, more appropriate therapy was instituted with a successful outcome.

Fatal pulmonary thromboembolism during total hip replacement under spinal anesthesia

Fatal pulmonary thromboembolism during total hip replacement under spinal anesthesia

Pharmacological Deep Vein Thrombosis Prophylaxis Does Not Lead to Hematoma Expansion in Intracerebral Hemorrhage With Intraventricular Extension

Patients with intracerebral hemorrhage (ICH) are at high risk for development of deep venous thrombosis. Current guidelines state that low-dose subcutaneous low molecular weight heparin or unfractionated heparin may be considered at 3 to 4 days from onset. However, insufficient data exist on hematoma volume in patients with ICH before and after pharmacological deep venous thrombosis prophylaxis, leaving physicians with uncertainty regarding the safety of this practice. We identified patients from our stroke registry (June 2003 to December 2007) who presented with ICH only or ICH+intraventricular hemorrhage and received either low molecular weight heparin subcutaneously or unfractionated heparin within 7 days of admission and had a repeat CT scan performed within 4 days of starting deep venous thrombosis prophylaxis. We calculated the change in hematoma volume from the admission and posttreatment CTs. Hematoma volume was calculated using the ABC/2 method and intraventricular hemorrhage volumes were calculated using a published method of hand drawn regions of interest. We identified 73 patients with a mean age of 63 years and median National Institutes of Health Stroke Scale score 11.5. The mean baseline total hematoma volume was 25.8 mL±23.2 mL. There was an absolute change in hematoma volume from pre- and posttreatment CT of -4.3 mL±11.0 mL. Two patients developed hematoma growth. Repeat analysis of patients given pharmacological deep venous thrombosis prophylaxis within 2 or 4 days after ICH found no increase in hematoma size. Pharmacological deep venous thrombosis prophylaxis given subcutaneously in patients with ICH and/or intraventricular hemorrhage in the subacute period is generally not associated with hematoma growth.

Heparin-Induced Increase in Serum Levels of Aminotransferases

Sixty-four patients over the age of 40 years, undergoing elective surgery of at least one hour's duration, were randomized to treatment with either a thromboembolic deterrent ( TED ) stocking (Kendall Co.) or subcutaneous low-dose heparin 5 000 IU every 12 hours. Serum levels of alanine aminotransferase (S-ALAT), aspartate aminotransferase (S-ASAT), gamma-glutamyl transpeptidase (S-gamma-GT) and alkaline phosphatase (S-ALP) were measured. S-ALAT increased significantly on the 5th and 10th postoperative day, from 27 +/- 2 (x +/- SE) to 40 +/- 4 (p less than 0.01) and 55 +/- 7 U/l (p less than 0.001), respectively, in the heparin group and was significantly higher in the heparin than in the TED group both on the 5th (p less than 0.01) and 10th (p less than 0.05) postoperative day. S-ASAT and S-gamma-GT increased significantly during heparin treatment, but did not differ significantly from the values of the TED group. No change in S-ALP was registered in either group. It is concluded that prophylactic treatment with low-dose heparin induces a significant increase in S-aminotransferase levels, especially in S-ALAT. The phenomenon has profound differential diagnostic implications in conditions such as pulmonary embolism and acute myocardial infarction.

Effects of low-dose subcutaneous heparin on the occurrence of deep vein thrombosis in patients with ischemic stroke.

The effectiveness of low-dose subcutaneous heparin in the prophylaxis of deep vein thrombosis in patients with ischemic stroke was investigated in an unblinded controlled study. The frequency of deep vein thrombosis and pulmonary embolism in the control group was 23% versus 2% in the patients receiving heparin. There were no bleeding complications in the test group and there were no differences in the occurrence of hemorrhage changes in the cerebral ischemic infarction in both groups.

Antithrombotic and Thrombolytic Therapy for Ischemic Stroke: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)

This article about treatment and prevention of stroke is part of the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patients' values may lead to different choices (for a full understanding of the grading, see the "Grades of Recommendations" chapter by Guyatt et al, CHEST 2008; 133:123S-131S). Among the key recommendations in this chapter are the following: For patients with acute ischemic stroke, we recommend administration of IV tissue plasminogen activator (tPA) if treatment is initiated within 3 h of clearly defined symptom onset (Grade 1A). For patients with acute ischemic stroke of > 3 h but < 4.5 h, we suggest clinicians do not use IV tPA (Grade 2A). For patients with acute stroke onset of > 4.5 h, we recommend against the use of IV tPA (Grade 1A). For patients with acute ischemic stroke who are not receiving thrombolysis, we recommend early aspirin therapy (Grade 1A). For acute ischemic stroke patients with restricted mobility, we recommend prophylactic low-dose subcutaneous heparin or low-molecular-weight heparins (Grade 1A). For long-term stroke prevention in patients with noncardioembolic stroke or transient ischemic attack (TIA) [ie, atherothrombotic, lacunar, or cryptogenic], we recommend treatment with an antiplatelet agent (Grade 1A), including aspirin (recommended dose, 50-100 mg/d), the combination of aspirin and extended-release dipyridamole (25 mg/200 mg bid), or clopidogrel (75 mg qd). In these patients, we recommend use of the combination of aspirin and extended-release dipyridamole (25/200 mg bid) over aspirin (Grade 1A) and suggest clopidogrel over aspirin (Grade 2B), and recommend avoiding long-term use of the combination of aspirin and clopidogrel (Grade 1B). For patients who are allergic to aspirin, we recommend clopidogrel (Grade 1A). In patients with atrial fibrillation and a recent stroke or TIA, we recommend long-term oral anticoagulation (target international normalized ratio, 2.5; range, 2.0 to 3.0) [Grade 1A]. In patients with venous sinus thrombosis, we recommend unfractionated heparin (Grade 1B) or low-molecular-weight heparin (Grade 1B) over no anticoagulant therapy during the acute phase.

Practice Guidelines for Deep Venous Thrombosis Prophylaxis in Burns

Measures to prevent deep venous thrombosis (DVT), including low-dose subcutaneous heparin, low molecular weight heparin, or sequential compression devices, may be considered in high-risk patients, specifically those with a previous history of thromboembolic disease, and in patients with significant burns of the lower extremities. The purpose of this guideline is to review the principles of prophylaxis for DVT in burn patients and to present a reasonable approach for the treatment of patients during burn resuscitation. This guideline is designed to aid those physicians who are responsible for the triage and initial management of burn patients. DVT in the burn patient is a more common event than previously reported, with incidence ranging from 1% to 23% in the few available series. The suspected risk of bleeding using low-dose heparin has deterred most burn surgeons from using heparin routinely in all burn patients. Much remains unknown, however, regarding the real risks and benefits of this complication and its treatment. A Medline search of all English language citations from 1966 through 2006 was undertaken using the key words "deep vein thrombosis" and "deep venous thrombosis" with "burns." This produced 18 references. The addition of the key words "pulmonary embolism" with "burns" produced a total of 82 references, of which 7 were felt to be relevant to this topic based on evidentiary classification of the data. There are no prospective, randomized, controlled studies evaluating the effectiveness of any prophylactic preventive measures against DVT in burn patients. The apparently low incidence of this condition in burn patients would appear to preclude its evaluation in a single-center study, and no multicenter studies have been conducted.

Systemic Anticoagulant Effect of Low-Dose Subcutaneous Unfractionated Heparin as Determined Using Thrombelastography

In an observational study using heparinase-modified thrombelastography, we investigated the percentage of elective cardiothoracic surgical patients receiving low-dose unfractionated heparin (5000 IU 12 hourly subcutaneously) who had a demonstrable systemic heparin effect. Blood samples were obtained at induction from 40 adult elective cardiothoracic surgical patients who had received 5000 IU unfractionated heparin subcutaneously within six hours. Simultaneous kaolin and heparinase-modified thrombelastographies were run on all samples. Fourteen patients (35%; 95% CI: 20 to 50%) had a demonstrable heparin effect (defined as a kaolin thrombelastography R time >25% longer than the heparinase-modified control). Their mean +/- SD kaolin thrombelastography R time was 13.6 +/- 5.9 minutes (normal range 4 to 8 minutes) vs. 7.1 +/- 2.0 minutes for the heparinase-modified controls. In 10 patients the thrombelastography R times were >50% longer and in four patients >100% longer than their respective heparinase-modified controls. In a post hoc analysis, there was little correlation between the extent of the prolongation and patient age (r = 0.02), weight (r = -0.31), preoperative creatinine (r = -0.17), or time since administration of heparin (r = 0.14). These results indicate that about one third of patients who have received low-dose unfractionated heparin subcutaneously within six hours have a demonstrable heparin effect. The potential for this effect should be considered if central neural blockade is planned.

Antiphospholipidantikörpersyndrom: a priori eine Kontraindikation zur Nierentransplantation?

The antiphospholipid antibody syndrome (APLS) is characterised by the presence of antiphospholipid antibodies in association with thrombotic disorders of the arterial and/or venous system, spontaneous abortion and thrombocytopenia. Several studies have shown that end-stage renal disease patients with APLS are at extremely high risk for graft thrombosis and graft loss after kidney transplantation. We report on the treatment and clinical courses of 6 APLS renal transplant patients. Of 3 patients treated with low-dose subcutaneous heparin two had early graft loss due to venous graft thrombosis; of those patients treated by systemic heparin (PTT goal 45-55 s) and followed by coumadin (INR 2.5-3.0) only one had early graft loss whereas 2 grafts are doing well 2 years post-transplant. Our experience as well as recently published data suggest that kidney transplantation can be performed successfully in APLS patients if anticoagulation therapy is performed consistently. A general APL antibody screening prior to kidney transplantation does not seem to be justified at present. A prospective, randomised multicenter study is warranted to evaluate the management of these patients with respect to intensity, type and duration of anticoagulation therapy.

Prevention of venous thromboembolism

The aim of prophylaxis in venous thromboembolism is firstly to prevent fatal pulmonary embolism and secondly to reduce the morbidity associated with deep vein thrombosis and the post-phlebitic limb. Particularly high-risk groups are identifiable and include those over 60 years of age undergoing major surgery, patients with malignancy and those undergoing hip operations. Low-dose subcutaneous heparin (5000 U s.c. commenced two hours preoperatively and continued eight to twelve hourly until the patient is fully mobile) is unequivocally effective in preventing deep vein thrombosis in medical and surgical patients and, most importantly, significantly reduces the incidence of fatal postoperative pulmonary embolism and total mortality. Furthermore, in established deep vein thrombosis, low-dose heparin limits proximal clot propagation, which is the prelude to pulmonary embolism. Despite this, surveys have demonstrated an alarming deficiency amongst clinicians in the application of measures to prevent venous thromboembolism. Heparin prophylaxis carries a small risk of increased bleeding complications, mostly evidenced by the frequency of wound haematoma rather than major haemorrhage. Low molecular heparin fragments (e.g. Fragmin, Choay, Enoxaprin) are now emerging as useful alternative agents, having the advantage of once daily administration and yet providing similar efficacy in the prevention of deep vein thrombosis. However, protection against fatal pulmonary embolism has yet to be demonstrated. Mechanical methods of prophylaxis designed to counteract venous stasis, such as graduated elastic compression stockings, are also beneficial in protection against deep vein thrombosis but by themselves do not achieve such consistently good prophylaxis as low-dose heparin. However, clinical trials with combinations of mechanical methods and low-dose heparin indicate that this may be the optimum approach to very high-risk patients. In the presence of established acute deep vein thrombosis, anticoagulant therapy is the mainstay in preventing pulmonary embolism. Vena caval interruption procedures should be reserved for patients in whom anticoagulation is contraindicated or for those who develop recurrent pulmonary embolism despite adequate anticoagulation.

Safety and efficacy of concurrent application of oral pentosan polysulfate and subcutaneous low-dose heparin for patients with interstitial cystitis

Objectives To conduct a prospective controlled study assessing the safety and efficacy of the additional administration of subcutaneous low-dose heparin in patients receiving oral pentosan polysulfate (PPS) medication for interstitial cystitis. Methods A total of 41 patients with interstitial cystitis who reported efficacy of oral PPS medication were divided into three groups (major, intermediate, and minor PPS response), according to their therapeutic response to PPS. Patients received 3 × 5000 IU/day heparin for 2 days, followed by 2 × 5000 IU/day for 12 days. The maintenance dose was 5000 IU/day heparin. We used 17 patients randomly taking PPS alone as the control group. The primary endpoint was a change in overall well-being. Secondary endpoints were changes in pain, urgency, frequency, functional bladder capacity, and the O’Leary-Sant index. Results Overall, 10 patients were identified as responders at 3 months (24.4%) and 9 patients at 6 months (21.9%) compared with no responders in the control group ( P ≤0.001). At 3 months, 7 (31.8%) of 22 patients in the minor response group reported a statistically significant overall improvement in their well-being compared with 1 (12.5%, P ≤0.001) of 8 patients of the intermediate group and 2 (18.2%, P ≤0.001) of 11 patients of the major response group. A significant amelioration of pain intensity was observed in the minor response group at 3 and 6 months. Conclusions The concurrent administration of low-dose heparin and oral PPS appears to be a safe and efficacious treatment modality. The subcutaneous administration of heparin appeared to be predominantly of value for patients with interstitial cystitis and an initial minor response to PPS.

A review of the risks and benefits of differing prophylaxis regimens for the treatment of deep venous thrombosis and pulmonary embolism in neurosurgery

Background Annually, 2 million people in the United States develop deep venous thrombosis (DVT), and nearly 100 000 sustain fatal pulmonary emboli. Prophylaxis against DVT/pulmonary embolism (PE) is a critical issue, and options include elastic stockings, intermittent pneumatic compression stockings, low-dose unfractionated heparin (5000 U every 8-12 hours), and low molecular-weight heparin (ie, enoxaparin and dalteparin). The risks and benefits associated with different prophylaxis regimens used in the prevention of DVT and PE in neurosurgical procedures were analyzed. Methods Neurosurgical studies focusing on different methods of prophylaxis used for the prevention of DVT and PE were reviewed. The efficacy, risks, and benefits of varied treatment options were evaluated, with particular emphasis on minor and major hemorrhages occurring where heparin-based protocols were used. Results In Flinn et al series ( Arch Surg. 1996;131(5):472-80), the incidence of DVT was greater for cranial (7.7%) than spinal procedures (1.5%). Although intermittent pneumatic compression devices provided adequate reduction of DVT/PE in some cranial and combined cranial/spinal series, low-dose subcutaneous unfractionated heparin or low molecular-weight heparins further reduced the incidence, not always of DVT, but of PE ( Br J Neurosurg 1995;9(2):159-63; J Intensive Care Med 2003;18(2):59-79). Nevertheless, low-dose heparin-based prophylaxis in cranial and spinal series risks minor and major postoperative hemorrhages: 2% to 4% in a cranial series, 3.4% minor and 3.4% major hemorrhages in a combined cranial/spinal series, and a 0.7% incidence of major/minor hemorrhages in a spinal series ( J Neurosurg 2003;99(4):680-4; Neurosurgery 1986;18(4):440-5; Eur Spine J 2004;13(1):1-8; J Intensive Care Med 2003;18(2):59-79). Conclusions Although mechanical prophylaxis provided effective prophylaxis against DVT/PE in many series, the added efficacy of low-dose heparin regimens has to be weighed against risks of major postoperative hemorrhages and their neurological sequelae.

Left ventricular apical thrombus after systemic thrombolysis with recombinant tissue plasminogen activator in a patient with acute ischemic stroke

BackgroundThrombolysis with recombinant tissue plasminogen activator (rtPA) is an established treatment in acute stroke. To prevent rethrombosis after rtPA therapy, secondary anticoagulation with heparin is commonly performed. However, the recommended time-point and extent of heparin treatment vary and are not well investigated.Case presentationWe report a 61-year-old man who developed an acute global aphasia and right-sided hemiparesis. Cranial CT was normal and systemic thrombolytic therapy with tPA was started 120 minutes after symptom onset. Low-dose subcutaneous heparin treatment was initiated 24 hours later. Transthoracic echocardiography (TTE) 12 hours after admission showed slightly reduced left ventricular ejection fraction (LVEF) but was otherwise normal. 48 hours later the patient suddenly deteriorated with clinical signs of dyspnea and tachycardia. TTE revelead a large left ventricular apical thrombus as well as a reduction of LVEF to 20 %. Serial further TTE investigations demonstrated a complete resolution of the thrombus and normalisation of LVEF within two days.ConclusionOur case demonstrates an intracardiac thrombus formation following rtPA treatment of acute stroke, probably caused by secondary hypercoagulability. Rethrombosis or new thrombus formation might be an underestimated complication of rtPA therapy and potentially explain cases of secondary stroke progression.