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At least 19 recordsLinked to original sources

PubMed1997

Emergency oral anticoagulant reversal: the relative efficacy of infusions of fresh frozen plasma and clotting factor concentrate on correction of the coagulopathy.

Haemorrhage, including intracranial bleeding, is a common, potentially lethal complication of warfarin therapy and rapid and complete reversal of anticoagulation may be life-saving. Fresh frozen plasma (FFP) and vitamin K are most frequently administered. Because of the variable content of vitamin K-dependent clotting factors in FFP, and the effects of dilution, the efficacy of this approach is open to doubt. We have therefore compared the effects of FFP and clotting factor concentrates on the INRs and clotting factor levels of orally anticoagulated subjects requiring rapid correction of their haemostatic defect. In many, the pre-treatment INR was considered to be dangerously above the target therapeutic range. In the 12 patients given FFP, the INR did not completely correct (range 1.6-3.8, mean 2.3) indicating an ongoing anticoagulated state in all. In contrast, the INR in 29 subjects given clotting factor concentrates was completely corrected in 28 (range 0.9-3.8, mean 1.3). Following treatment, marked differences were observed in clotting factor IX levels between the two groups. The median factor IX level was 19 u/dl (range 10-63) following FFP infusion and 68.5 u/dl (range 31-111) following concentrate. In FFP treated patients, poorer responses were also observed for each of the other vitamin K-dependent clotting factors but these were less marked than for factor IX, which was present in low concentrations in some batches of FFP. Thus, haemostatically effective levels of factor IX cannot be achieved, in most instances, by the conventional use of FFP in patients requiring reversal of their anticoagulant therapy. Clotting factor concentrates are the only effective option where complete and immediate correction of the coagulation defect is indicated in orally anticoagulated patients with life or limb-threatening haemorrhage.

Administration, Oral↗

PubMed1993

Efficacy and toxicity of differently charged polycationic protamine-like peptides for heparin anticoagulation reversal.

PURPOSE: The role of total cationic charge of synthetic protamine-like peptides in heparin anticoagulation reversal and accompanying adverse hemodynamic effects was studied. METHODS: Five protamine variants having specific total charges of [+8], [+16], [+18], [+20], and [+21] were synthesized by fluorenylmethoxycarbonyl procedures. Each of these lysine-containing peptides plus arginine-containing control salmine native protamine (n-protamine, [+21] charge) was studied in five dogs who received heparin 150 IU/kg intravenously followed by 1.5 mg/kg (intravenously during a 10-second period) of the synthesized peptide or control n-protamine. RESULTS: Anticoagulation reversal as assessed by a number of coagulation tests was more effective with peptides of greater cationic charge. In this regard, activated clotting time reversal 3 minutes after peptide administration was 7%, [+8]; 54%, [+16]; 81%, [+18]; 92%, [+20]; 81%, [+21]; and greater than 100% [n-protamine]. Reversal of heparin anticoagulation at 3 and 30 minutes, respectively, correlated significantly (*p < or = 0.05, p < or = 0.01 [see corresponding symbols within abstract]) with total cationic charge as assessed by activated clotting time (r = 0.97, 0.99 ), prothrombin time (r = 0.98, 0.87*), activated partial thromboplastin time (r = 0.99, 0.78), thrombin clotting time (r = 0.84,* 0.85*), heparin anti-Xa activity (r = 0.87,* 0.85*), and heparin anti-IIa activity (r = 0.79 at 3 minutes, p = 0.06). Maximum declines in systemic mean arterial pressure (MAP) were greater with more positively charged peptides: -1 mm Hg, [+8]; -3 mm Hg, [+16]; -31 mm Hg; [+18]; -31 mm Hg, [+20]; -35 mm Hg, [+21]; and -34 mm Hg [n-protamine]. Maximum decreases in MAP, cardiac output, and systemic oxygen consumption were highly correlated (p < or = 0.05) with total cationic charge: MAP, r = 0.87; cardiac output, r = 0.87; and systemic oxygen consumption, r = 0.86. A total toxicity score, reflecting adverse hemodynamic effects, was greater with increasing charge: -1.9 +/- 1.1, [+8]; -2.7 +/- 0.8, [+16]; -6.6 +/- 3.3, [+18]; -6.1 +/- 3.5, [+20]; -6.9 +/- 3.8, [+21]; and -7.0 +/- 5.2 [n-protamine]. The correlation of mean peptide total toxicity score to total cationic charge was significant (r = 0.89, p < 0.05). CONCLUSIONS: These data suggest for the first time that effective alternatives to salmine protamine for reversal of heparin anticoagulation can be synthesized. Furthermore, total cationic charge appears to be an important determinant for both anticoagulation reversal and toxicity of protamine-like peptides.

Animals↗

PubMed1998

Clinical experience with the use of clotting factor concentrates in oral anticoagulation reversal.

We report the clinical experience of a large Haemophilia Centre and Haemostasis Unit in reversing oral anticoagulation (OAC) using clotting factor concentrates. This is a retrospective study extending over 2 years (January 1996-December 1997). Reversal was performed using a combination of factor IX and factor VII concentrates administered by intravenous infusion. in a dose varying between 12 i.u./kg and 50 i.u./kg. We identified 20 episodes of OAC reversal in 18 patients, with a prevalence of 10 reversal episodes/1000 OAC patients/year. The median age was 77 years old (range 53-92 years). Indications for OAC reversal were divided into major bleeds (muscle haematoma [9], haematuria [3], subarachnoid haemorrhage [1], oesophageal bleeding [1], haemoptysis [1], haemarthrosis [1]); minor bleeds (extensive bruising [9], epistaxis [3], oral cavity bleeding [1]); and emergency invasive investigation (2). Pre-reversal, the international normalized ration (INR) was greater than 6.0 in 15/18 patients. Post-infusion. there was an immediate reduction in the INR towards normal (mean 1.3; range 1.1-2.3). There were no thrombotic complications or other adverse effects. The median use of factor 9 A concentrate was 2300 units/patient (range 570-4195), at a cost of 645 Pounds/patient and for factor VII concentrate 2200 units/patient (range 815-3630), at a cost of 664 Pounds/patient. Clotting factor concentrates provide a safe, rapid and effective means for OAC reversal and although expensive it is the treatment of choice in the over anticoagulated, bleeding patient.

Aged↗

PubMedDate not supplied

Reversing anticoagulants both old and new.

PURPOSE: Reversal of pharmacologic anticoagulation is an issue that arises when an anticoagulated patient has major bleeding or when a patient on chronic anticoagulant therapy requires urgent reversal of anticoagulation, for example, for surgery. SOURCE: We reviewed the literature to determine what strategies are available to reverse anticoagulation caused by older agents, such as warfarin or unfractionated heparin (UFH), as well as newer agents, for example, low-molecular-weight heparin, danaparoid, fondaparinux, lepirudin, and argatroban. PRINCIPAL FINDINGS: Specific "antidotes" exist for the "classic" anticoagulant agents: protamine sulfate for UFH, and vitamin K for warfarin. However, vitamin K only begins to reverse warfarin's anticoagulant effect by four to six hours, so urgent situations additionally require blood products, such as plasma (fresh frozen or cryosupermatant plasma), prothrombin complex concentrates, or, possibly, recombinant factor VIIa. A growing problem arises from the increasing use of new anticoagulants that lack specific antidotes. For example, protamine sulfate reverses only about 60% of the anti-factor Xa activity of low-molecular-weight heparin, has negligible effects on danaparoid (a mixture of anticoagulant glycosaminoglycans used to treat heparin-induced thrombocytopenia) and fondaparinux (a novel synthetic antithrombin-binding pentasaccharide with exclusive anti-factor Xa activity approved in the United States for antithrombotic prophylaxis following orthopedic surgery). The new direct thrombin inhibitors (e.g., lepirudin, bivalirudin, argatroban) also have no specific antidote. CONCLUSION: Newer anticoagulant agents generally lack specific antidotes. Thus, careful choice of an anticoagulant agent and laboratory monitoring where appropriate are needed to minimize risk of bleeding complications.

Anticoagulants↗

PubMed2004

Impaired warfarin response secondary to high-dose vitamin K1 for rapid anticoagulation reversal: case series and literature review.

The literature suggests that unresponsiveness to warfarin can continue for 1 week or longer after administration of high-dose vitamin K1 10 mg or greater; however, there is a lack of supporting data to define the duration and clinical consequences of impaired warfarin response with high doses of vitamin K1. This case series describes four patients receiving indefinite warfarin therapy who received high and, in most cases, repeated doses of vitamin K1 for urgent reversal of therapeutic anticoagulation for an invasive procedure or surgery. The patients displayed impaired warfarin response for 11 days-3.5 weeks after administration of vitamin K1 10-40 mg. The associated financial burden for the patients was substantial. We reviewed the literature to examine the mechanism of impaired warfarin response, and the clinical efficacy, safety, and appropriateness of vitamin K1 and fresh-frozen plasma in urgent reversal of anticoagulation.

Adult↗

PubMed1998

Prospective evaluation of anticoagulant reversal with oral vitamin K1 while continuing warfarin therapy unchanged.

STUDY OBJECTIVES: To study the efficacy and safety of partially correcting therapeutic anticoagulation by administering oral vitamin K1. DESIGN: Prospective interventional trial. SETTING: Outpatient anticoagulation clinic. PATIENTS: Patients who required reversal of their normal or excessive therapy with oral anticoagulant drugs were recruited. INTERVENTIONS: All patients received a single oral dose of vitamin K1. The dose was calculated using a regression formula and was intended to decrease the international normalized ratio (INR) to a predetermined value. Patient follow-up continued for 8 weeks. We compared the actual change of the INR to the predicted change. RESULTS: Sixty-five reversals of anticoagulant therapy were initiated in the study group. Sixty-four of the 65 reversals were successful. The mean (+/-SEM) initial INR was 2.6+/-0.1 for the preprocedure patients and 8.4+/-0.5 for the excessively anticoagulated patients. The predicted change in the INR correlated with the actual change (r = 0.92, p < 0.0001). There were no thromboembolic events and only one hemorrhagic complication. The mean (+/-SEM) dose of oral vitamin K1 was 5.0+/-0.3 mg for the preprocedure patients and 10.0+/-1.0 mg for the excessively anticoagulated patients. CONCLUSIONS: The administration of a single oral dose of vitamin K1 is a safe and effective method for partially reversing anticoagulant therapy without disrupting the daily maintenance dose of warfarin. A reliable regression formula was developed to predict the dose of vitamin K1 needed to achieve the desired INR.

Anticoagulants↗

PubMed1976

Comparison of prothrombin complex concentrate and vitamin K1 in oral anticoagulant reversal.

A randomised clinical trial was undertaken to compare the value of a factor II, IX, and X concentrate (Prothromplex) with intravenous vitamin K1 (2-5 mg) in reversing an overdose of oral anticoagulants. Rapid partial correction of the prothrombin time, partial thromboplastin time, and the clotting factor assays were observed with the concentrate, but these changes were not always sustained. In contrast vitamin K1 did not show any great effect at two hours but at 24 hours there was always over-correction despite the conservative dosage, prothrombin times being shorter than the therapeutic range. The prothrombin complex concentrate provides a quicker, more controlled but less sustained method of reversing the coumarin defect than vitamin K1. But there remains a significant risk of hepatitis even with a preparation for which strenuous efforts have been made to minimise this risk by screening for hepatitis B virus. The risk should be carefully considered before such concentrates are infused in non-urgent conditions.

Anticoagulants↗

PubMed2000

Prothrombin complex concentrate for oral anticoagulant reversal in neurosurgical emergencies.

The incidence of spontaneous intracranial haemorrhage has increased markedly in line with the increased use of oral anticoagulant agents. Recent guidelines for reversal of this acquired coagulation defect in an emergency have been established, but they are not adhered to in all centres. Our unit is referred between 20 and 60 patients per year (1994-1999) who are anticoagulated and require urgent neurosurgical intervention. In order to investigate this, we performed a prospective study using prothrombin complex concentrate (PCC). PCC was given to the first six patients with intracranial haemorrhage admitted to the neurosurgical unit requiring urgent correction of anticoagulation (Group 1) and compared with patients receiving standard treatment with fresh frozen plasma and vitamin K (Group 2). Mean International Normalised Ratios of Group 1 were 4.86 pretreatment and 1.32 posttreatment, and of Group 2 were 5.32 and 2.30, respectively. Results for complete reversal and reversal time were significant for PCC with p < 0.001. We recommend PCC for rapid and effective reversal of warfarin in life-threatening neurosurgical emergencies.

Adult↗

PubMed2005

Rapid warfarin reversal in anticoagulated patients with traumatic intracranial hemorrhage reduces hemorrhage progression and mortality.

BACKGROUND: A prospective cohort study at our institution demonstrated a 48% mortality rate in warfarin anticoagulated trauma patients sustaining intracranial hemorrhage (ICH) compared with a 10% mortality rate in nonanticoagulated patients. Forty percent of patients demonstrated progression of their ICH, despite anticoagulation reversal, with a resultant 65% mortality rate. Seventy-one percent of these patients initially presented with a Glasgow Coma Scale (GCS) score > or = 14 and a 'minor' ICH. We postulated that early diagnosis of ICH and rapid anticoagulation reversal would reduce ICH progression rates and mortality. METHODS: All anticoagulated patients with known or suspected head trauma were entered into the Coumadin protocol. The protocol ensured immediate triage and physician evaluation, head computed tomography (CT) scan, and fresh frozen plasma administration in patients with documented ICH. RESULTS: Eighty-two patients were entered into the protocol with ICH documented in 19 (23%). Sixteen of 19 patients (84%) presented with GCS > or = 14. Median international normalized ratio (INR) for treated patients with ICH was 2.7 versus 2.5 for patients without ICH (p = 0.546). Mean time to initiate warfarin reversal was 1.9 hours for protocol patients versus 4.3 hours for preprotocol patients (p < 0.001). Two of 19 (10%) protocol patients with ICH died. However, both patients presented >10 hours after injury with a severe ICH. This 10% mortality rate is significantly less than the 48% mortality rate seen previously (p < 0.001) and is now consistent with that observed in similarly injured patients not on anticoagulation. CONCLUSION: Neither the initial GCS nor INR in anticoagulated trauma patients reliably identifies patients with ICH. Rapid confirmation of ICH with expedited head CT scan combined with prompt reversal of warfarin anticoagulation with fresh frozen plasma decreases ICH progression and reduces mortality.

Aged↗

PubMed1999

Anticoagulation and anticoagulation reversal with cardiac surgery involving cardiopulmonary bypass: an update.

Accelerated thrombin generation is central to the development of hemostatic abnormalities during cardiopulmonary bypass (CPB) that are associated with both thromboembolic complications and serious, abnormal bleeding. Thrombin not only converts fibrinogen to fibrin, but also activates platelets and coagulation factors V, VIII, and XI and causes release of von Willebrand factor from vascular endothelium. Thrombin can also downregulate the hemostatic system by inducing formation of platelet inhibitory agents, such as nitric oxide and prostacyclin, and release of tissue plasminogen activator, facilitating activation of protein C, and releasing tissue factor pathway inhibitor. Excessive thrombin activity may also result in substantial consumption of platelets, fibrinogen, and labile coagulation factors and abnormal bleeding. Elevated tissue plasminogen activator levels secondary to activation of the contact system and surgery catalyze the formation of plasmin, which also consumes or internalizes platelet glycoprotein receptors and coagulation factors V, VIII, and fibrinogen. Heparin can reduce the generation of and mediate neutralization of excessive and CPB-associated thrombin activity. Heparin anticoagulation is commonly monitored with the activated clotting time (ACT). However, the ACT may be prolonged by factors other than heparin during CPB, such as hemodilution and hypothermia, and therefore may not accurately reflect the extent of anticoagulation by heparin. Aprotinin, a nonspecific serine protease inhibitor used with CPB, can also prolong celite-based ACT values, rendering it less reliable for monitoring heparin anticoagulation. Therefore, several alternative anticoagulation strategies have been recommended when aprotinin is used, such as a higher celite ACT trigger (>750 seconds), monitoring of whole blood heparin concentrations (eg, >2.7 U/mL), or administration of heparin based on a CPB duration-dependent, fixed-dose regimen. Administration of heparin doses higher than those generally recommended, as guided by predetermined, patient-specific whole blood heparin concentration measurements during bypass, can reduce excessive thrombin-mediated consumption of platelets and coagulation factors as well as post-CPB blood loss and blood component transfusions. New modalities of improving suppression of excess thrombin generation during CPB include use of heparin-bonded CPB circuits, heparin cofactor II or related analogs, supplemental antithrombin III, direct thrombin inhibitors (eg, hirudin, argatroban), and inhibitors of the contact and tissue factor pathways. The safety and efficacy of these approaches remains to be established by additional, appropriately powered, prospective studies.

Anticoagulants↗

PubMed2005

Impact of introducing guidelines on anticoagulant reversal.

The production of clinical guidelines has become an accepted and lauded part of modern medicine. It is also widely perceived that these guidelines provide some sort of panacea for the problems that medicine faces. Our experience suggests otherwise. Triggered by on going anecdotal evidence of poor practice, we reviewed the effect on practice of a recently introduced local guideline on the management of major bleeding in patients on warfarin. Comparing 34 patients treated before and 48 patients after the introduction of the guideline, we found no significant improvement in prothrombin complex concentrate dosing or administration of vitamin K. The only improvement witnessed was in early assessment of the effect of the intervention on coagulation which improved from 10 to 35% of cases. Of major concern, in 10% of cases, there was no documentation to confirm or refute that prothrombin complex concentrate (PCC), which had been issued, had actually been administered to the patient. The production and widespread dissemination of this local guideline did not achieve significant improvement in clinical practice. Possible reasons for failure to adhere to the guideline are discussed.

Anticoagulants↗

PubMed1994

At high heparin concentrations, protamine concentrations which reverse heparin anticoagulant effects are insufficient to reverse heparin anti-platelet effects.

Combined effects of heparin and protamine on plasma clot structure and platelet function were studied. Anticoagulant effects were monitored as changes in aPTT. Clot structure was defined in terms of fibrin fiber mass/length ratio (mu) and clot elastic modulus (EM). Platelet function was studied utilizing platelet aggregation and platelet force development (PFD) measurements. Heparin (1 U/ml) prolonged the aPTT from 30 to > 300 seconds, reduced PFD from 5,100 to 0 dynes, decreased mu (in batroxobin-induced gels) from 1.36 to 1.08 x 10(13) daltons/cm and decreased clot EM from 9,600 to 2000 dynes/cm2. Varying amounts of protamine reversed these effects: 16 micrograms/ml normalized the aPTT, 20 micrograms/ml normalized PFD, 32 micrograms/ml corrected mu, and 20 micrograms/ml returned EM to baseline. At high heparin concentrations (4 U/ml), protamine concentrations which corrected anticoagulant effects were inadequate to reverse antiplatelet effects. A protamine concentration of 40 micrograms/ml normalized the aPTT and mu, but 140 micrograms/ml of protamine was required to reverse heparin suppression of force development and clot elastic modulus. Excess protamine inhibited clotting and platelet function. In plasma containing 1 u heparin/ml, 140 micrograms protamine/ml reduced PFD by 83%, prolonged the aPTT by 63%, and reduced clot EM by 75%. In heparin free plasma, > 75 micrograms protamine/ml prolonged the aPTT. Thus, platelet function and clot structure are sensitive to protamine during heparin neutralization, and anti-platelet effects of heparin may persist when the aPTT is completely corrected. Excess protamine inhibits platelet function and compromises clot structure.

Blood Coagulation↗

PubMed1991

Absence of complement-mediated events after protamine reversal of heparin anticoagulation.

Protamine reversal of heparin anticoagulation is associated with adverse hemodynamic effects that may be attenuated with protamine pretreatment (PP). This study assesses the role of complement activation during these phenomena in adult cardiac surgery patients. Sixteen individuals undergoing cardiopulmonary bypass were given intravenous normal saline or protamine (2 mg/kg) as a randomized pretreatment prior to undergoing heparin anticoagulation (400 IU/kg), coronary artery revascularization, and subsequent reversal of the anticoagulated state with protamine (4 mg/kg). Blood pressure, pulmonary artery diastolic pressure (PAD), heart rate, and cardiac output (CO) were measured during and after pretreatment, prior to heparin reversal by protamine, and for 10 min after reversal. Total hemolytic complement (CH50), C3 conversion to C3b, C3a/C5a, platelet count, and white blood cell count (WBC) were also measured at the same time periods. No significant correlation existed between complement activation and hemodynamic events, as might have been evident by decreased CH50, increased C3 conversion to C3b, or elevations in C3a/C5a levels. PP significantly prevented the CO decrease occurring at 1 and 3 min following heparin reversal by protamine (-0.8 and -1.4 liters/min vs 0.1 and -0.2 liters/min, P less than 0.05 and P less than 0.01, respectively). Reversal hypotension was less with PP, although PAD fell equally in both groups. WBC decreases after heparin reversal were less after PP (-25% vs -7%, P = 0.06). These data support the conclusion that, contrary to earlier reports, adverse hemodynamic and hematologic responses accompanying protamine reversal of heparin anticoagulation do not appear to be correlated with activation of complement. In fact, those patients having the greatest C3a generation exhibited the least hemodynamic changes.

Adult↗

PubMed2000

Temporary reversal of anticoagulation using oral vitamin K.

Brief reversal of oral anticoagulant therapy is frequently necessary prior to minor surgery or invasive procedures. We sought to determine the effect of an oral dose of 2.0 mg of vitamin K(1) on the international normalized ratio (INR) among patients with a stable therapeutic INR who were maintained on their daily dose of warfarin. We prospectively studied a convenience cohort of patients attending an anticoagulation clinic who had either just completed treatment for venous thromboembolism or were receiving prophylaxis for atrial fibrillation, cardiomyopathy, or peripheral vascular disease. Each patient received an oral dose of 2.0 mg of aqueous vitamin K(1). Serial INR measurements were taken over 1 week. There was wide variation in the INR response between patients, from no change to complete reversal of anticoagulation. The effect also varied widely over time. There was a significant inverse correlation between the fall in logarithm of the INR and the daily warfarin dose required to achieve an INR value of 2.5 (r=-0.52, p=0.011). Use of a 2.0 mg oral dose of vitamin K(1) does not reliably reverse (correct) a therapeutic INR in patients maintained on their daily dose of warfarin.

Administration, Oral↗

PubMed1998

Comparing different routes and doses of phytonadione for reversing excessive anticoagulation.

BACKGROUND: Significant controversy exists concerning how best to reverse excessive anticoagulation (due to warfarin sodium therapy) with phytonadione (vitamin K1) while avoiding overcorrection in patients who need to have anticoagulation therapy maintained. METHODS: A retrospective review of phytonadione use in reversing excessive anticoagulation was performed in 3 institutions. The effectiveness of low-dose (< or =0.5 mg) intravenous (LDIV), high-dose (1-10 mg) intravenous (HDIV), subcutaneous (1-10 mg) (SC), and oral (2.5 or 5 mg) (PO) phytonadione was evaluated within 48 hours of administration. Anticoagulation correction (international normalized ratio [INR], > or =2.0 and < or =5.0) occurred in 5 of 8 patients in the LDIV, 5 of 9 in the HDIV, 7 of 10 in the SC, and 5 of 6 in the PO groups. Correction was inadequate (INR >5.0) in 2 of 8 patients in the LDIV, 0 of 9 in the HDIV, 3 of 10 in the SC, and 1 of 6 in the PO groups. Overcorrection (INR <2.0) occurred in 1 patient in the LDIV, 4 patients in the HDIV, 0 in the SC, and 0 in the PO groups. CONCLUSIONS: Anticoagulation correction was achieved in most patients in all 4 groups. The HDIV method was most effective in lowering the INR to less than 5.0, but overcorrection occurred more frequently (4 patients in the HDIV vs 1 patient in the LDIV and 0 patients in the SC and PO groups). Failure to achieve an INR of less than 5.0 was a greater problem in the SC group (3 patients in the SC vs 2 patients in the LDIV and 1 patient in the PO groups). The LDIV and PO methods appear to be acceptable alternatives to the HDIV and SC methods currently recommended.

Administration, Oral↗

PubMed1987

Haemodynamic and haematologic alterations with protamine reversal of anticoagulation: comparison of standard heparin and a low molecular weight heparin fragment.

Reversal of anticoagulation with protamine sulfate causes many adverse haemodynamic and haematologic effects which could be due to differences in the mechanism of action of standard and low molecular weight heparin. Three groups of dogs were investigated: one group received normal saline pretreatment followed by heparinisation with standard heparin 150 IU/kg followed by protamine sulfate reversal 1.5 mg/kg after aortic interposition grafting: the second group were given normal saline pretreatment followed by heparinisation with low molecular weight heparin 150 U antiXa/kg and after grafting protamine sulfate reversal 1.5 mg/kg. The third group were given protamine sulfate pretreatment 2.25 mg/kg followed by low molecular weight heparin 150 U antiXa/kg and later protamine sulfate reversal 1.5 mg/kg after grafting. The same haemodynamic changes were seen regardless of the type of heparin or pretreatment with protamine given along with low molecular weight heparin. There was a suggestion that regular heparin cause a more pronounced increase in pulmonary artery pressure and a decrease in heart rate. On the other hand the systemic hypotension and reduction of cardiac output seemed more pronounced in the low molecular weight heparin group. Platelet count decreased less in the low molecular weight heparin group, but white blood cell count was equally reduced. Pretreatment with protamine did not abolish the adverse effects of protamine when reversing anticoagulation achieved with low molecular weight heparin, a finding not shared with standard heparin-protamine interactions.

Animals↗

PubMed1992

Emergency reversal of anticoagulation after intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Although intracerebral hemorrhage is one of the most serious complications during oral anticoagulant therapy, there are no guidelines on emergency treatment with respect to reversal of anticoagulation effect in these patients. METHODS: We retrospectively compared laboratory data and clinical features in 17 cases of anticoagulant-related intracerebral hemorrhage treated with prothrombin complex concentrate (n = 10) or fresh-frozen plasma (n = 7). RESULTS: In the group of patients treated with prothrombin complex concentrate, the mean prothrombin time decreased from 2.83 to 1.22 International Normalized Ratio within 4.8 hours, compared with a decrease from 2.97 to 1.74 within 7.3 hours in those given fresh-frozen plasma (i.e., four to five times more rapidly after treatment with prothrombin complex concentrate) (p less than 0.001). Symptoms and signs of intracerebral hemorrhage, measured on an eight-graded Reaction Level Scale, progressed on average 0.2 grades in patients given prothrombin complex concentrate compared with 1.9 grades in those given fresh-frozen plasma (p less than 0.05). In patients with prothrombin values above 1.46, clinical progression within 12 hours occurred in five of six cases. CONCLUSIONS: Treatment with prothrombin complex concentrate reverses anticoagulation more rapidly than fresh-frozen plasma, which might be of importance for the prevention of further bleeding.

Aged↗

PubMed1997

Comparison of the hemodynamic and hematologic toxicity of a protamine variant after reversal of low-molecular-weight heparin anticoagulation in a canine model.

Using the dog as an animal model, we developed an experimental preparation to compare hemodynamic and hematologic toxicity of anticoagulation reversal. Currently, protamine sulfate reversal of standard unfractionated heparin and low-molecular-weight heparin (LMWH) anticoagulation causes adverse side effects, including decreased systemic mean arterial pressure (MAP), decreased cardiac output (CO), decreased oxygen consumption (VO2), and thrombocytopenia. In addition, standard protamine is only marginally effective at reversing the factor Xa inhibition induced by LMWHs. We have produced protamine-like variant peptides to decrease the adverse responses attributed to standard protamine. The hemodynamic, hematologic, and coagulation effects of standard protamine and the protamine variant (+18RGD) were assessed after reversal of LMWH anticoagulation in anesthetized dogs. Flow probes and vascular catheters were surgically implanted for measurement of hemodynamic parameters including MAP, CO, VO2, and heart rate (HR). Hematologic studies (platelet and white blood cell counts) and coagulation studies (activated clotting time [ACT], activated partial thromboplastin time [aPTT], thrombin clotting time [TCT], antifactor Xa and antifactor IIa values) also were performed. The protamine variant +18RGD was less toxic, induced less thrombocytopenia, and was more effective in anticoagulation reversal than was standard protamine sulfate. Results of this study indicate that the dog may be a useful model for investigating important hemodynamic, hematologic, and coagulation parameters during reversal of LMWH anticoagulation by use of synthetic protamine variants.

Animals↗