Therapeutic Doses Of Heparin Research Articles

Risk-based secondary prevention of obstetric antiphospholipid syndrome

Treatment of pregnant women with antiphospholipid syndrome (APS) should be set apart from that from thrombotic APS patients. Patients with a history of pregnancy morbidity but no vascular thrombosis are usually treated with a prophylactic dose of heparin plus low-dose aspirin; whereas, those with previous vascular thrombosis alone or associated with previous pregnancy morbidity, are commonly treated with a therapeutic dose of heparin generally combined with low-dose aspirin. However, in about 20% of pregnant APS women these regimens fail. In this context, we conducted a case-control study on a large multicentre cohort of conventionally treated pregnancies to verify whether specific laboratory profiles and/or clinical characteristics are predictive of unsuccessful pregnancy outcome during conventional treatments. Multivariate analysis showed that pregnancy failure during conventional therapies was independently associated with a history of both thrombosis and pregnancy morbidity, the presence of systemic lupus erythematosus (SLE) or other systemic autoimmune diseases and triple antiphospholipid antibody positivity. With the aim to discover the most effective and safe treatments in high-risk pregnant APS women a large-scale multicentre study focusing on the effect of treatments on pregnancy outcome in women with APS and further risk factors for pregnancy failure has been designed.

Thrombolysis or Anticoagulation for Cerebral Venous Thrombosis: Rationale and Design of the TO-ACT Trial

Endovascular thrombolysis, with or without mechanical clot removal, may be beneficial for a subgroup of patients with cerebral venous sinus thrombosis (CVT) who have a poor prognosis despite treatment with heparin. Published experience with endovascular thrombolysis is promising but only based on case series and not on controlled trials. The objective of the Thrombolysis or Anticoagulation for Cerebral Venous Thrombosis (TO-ACT) trial is to determine if endovascular thrombolysis improves the functional outcome of patients with a severe form of CVT. The TO-A C T trial is a multicenter, prospective, randomized, open-label, blinded endpoint trial. Patients are eligible if they have a radiologically proven CVT, a high probability of poor outcome (defined by presence of one or more of the following risk factors: mental status disorder, coma, intracranial hemorrhagic lesion, or thrombosis of the deep cerebral venous system), and if the responsible physician is uncertain if endovascular thrombolysis or standard anticoagulant treatment is better. One hundred sixty-four patients (82 in each treatment arm) will be included to detect a 50% relative reduction (from 40% to 20%) of poor outcomes. Patients will be randomized to receive either endovascular thrombolysis or standard therapy (therapeutic doses of heparin). Endovascular thrombolysis is composed of local application of rt-plasminogen activator (PA) or urokinase within the thrombosed sinuses, mechanical thrombosuction, or a combination of both. Patients randomized to endovascular thrombolysis will be treated with heparin before and after the interventional procedure, according to international guidelines. The primary endpoint is the modified Rankin score (mRS) at 12 months, with a score ≥2 defined as poor outcome. Secondary outcomes are six-months mRS, mortality, and recanalization rate. Major intracranial and extracranial hemorrhagic complications within one-week after the intervention are the principal safety outcomes. Results will be analyzed according to the 'intention-to-treat' principle. Blinded assessors not involved in the treatment of the patient will assess endpoints with standardized questionnaires.

Heparin-induced Leukocytosis Requires 6-O-Sulfation and Is Caused by Blockade of Selectin- and CXCL12 Protein-mediated Leukocyte Trafficking in Mice

Leukocytosis refers to an increase in leukocyte count above the normal range in the blood and is a common laboratory finding in patients. In many cases, the mechanisms underlying leukocytosis are not known. In this study, we examined the effects, the structural determinants, and the underlying mechanisms of heparin-induced leukocytosis, a side effect occurring in 0.44% of patients receiving heparin. We observed that heparin induced both lymphocytosis and neutrophilia, and the effects required heparin to be 6-O-sulfated but did not require its anticoagulant activity. Cell mobilization studies revealed that the lymphocytosis was attributable to a combination of blockage of lymphocyte homing and the release of thymocytes from the thymus, whereas the neutrophilia was caused primarily by neutrophil release from the bone marrow and demargination in the vasculature. Mechanistic studies revealed that heparin inhibits L- and P-selectin, as well as the chemokine CXCL12, leading to leukocytosis. Heparin is known to require 6-O-sulfate to inhibit L- and P-selectin function, and in this study we observed that 6-O-sulfate is required for its interaction with CXCL12. We conclude that heparin-induced leukocytosis requires glucosamine 6-O-sulfation and is caused by blockade of L-selectin-, P-selectin-, and CXCL12-mediated leukocyte trafficking.

A New Rapid Test for the Detection of PF4:Heparin Antibodies.

AbstractAbstract 3708Heparin Induced Thrombocytopenia (HIT), the most frequent drug-induced immune-mediated type of thrombocytopenia, is an important and sometimes life-threatening complication of heparin therapy. HIT can be triggered by standard therapeutic dose heparin, low-dose (prophylactic treatment), low molecular weight heparin, unfractionated heparin and even by minute quantities given to flush intravascular catheters.HIT is a clinicopathologic syndrome cause by platelet activating antibodies that recognize complexes of platelet factor 4 and heparin (PF4-heparin). Thrombocytopenia occurring within 5 – 10 days of administration of heparin is the most common clinical effect. The most severe complication of HIT is the occurrence of both venous and arterial thrombosis. Venous thrombosis can result in limb gangrene and the need for limb amputation.The diagnosis of HIT is based on clinical abnormalities including thrombocytopenia with or without thrombosis and the detection of antibodies to the PF4-heparin complex (termed PF4 dependant antibodies). There are two major types of assays for the detection of heparin dependant antibodies: functional assays and PF4 dependant antigen immunoassays. Functional assays include the serotonin release assay (SRA) and the heparin induced platelet activation assay (HIPA). Enzyme linked immunoassays (ELISAs) are the most frequently used PF4 dependent antigen immunoassay. Functional assays are technically difficult to perform and are considered to be complex specialty assays. ELISAs while not complex are not generally available on a STAT basis. There is a need for a simpler assay which retains or improves the sensitivity and specificity of the existing immunoassays that can be available on a STAT basis.GTI Diagnostics is developing a rapid test based on the proprietary technology used in GTI's PF4 Enhanced® ELISA. The PF4 Rapid test is a single use, semi-quantitative assay contained in a cartridge. It is designed to detect anti-PF4-heparin antibodies in human serum and/or plasma with a total assay time of 15 minutes. The assay uses only 5 μL of human serum and/or plasma along with a proprietary antigen and a proprietary fluorescent secondary antibody used for detection. The assay results are read using a fluorescent reader. A method comparison study was conducted which included an evaluation of 83 serum samples obtained from patients receiving heparin of which 36 were positive and 22 were negative in the PF4 Enhanced® assay. These samples were also tested in the PF4 Rapid Test assay. In addition 25 samples from normal individuals who were not receiving heparin were tested in both assays. Analysis of the data using a 2×2 table (shown below) resulted in a sensitivity of 100%, a specificity of 93.6% and an overall agreement of 96.4% of the PF4 Rapid Test compared to the PF4 Enhanced®.PF4 Enhanced® ELISAPositiveNegativeTotalPF4 Rapid TestPositive36339Negative04444Total364783Although HIT is a true clinicopathological syndrome, its diagnosis still rests primarily on clinical grounds since laboratory tests may not be available locally or may not be available in a sufficiently timely manner. Owing to the high risk of thrombosis associated with HIT, antithrombotic therapy with alternative anticoagulants should be started immediately when serologic assays confirm clinical suspicion. Readily available results, obtained from immunoassays for rapid detection of antibodies against PF4-heparin complexes, may be combined with the pretest estimation of clinical probability in order to exclude and/or confirm the diagnosis of HIT; therefore, assisting physicians in the time-sensitive clinical management of HIT. Disclosures:Ladvienka:GTI Diagnostics, Inc: Employment. Visentin:GTI Diagnostics, Inc: Employment. Chance:GTI Diagnostics, Inc: Employment.

Postoperative Spinal Epidural Hematoma

Surgeon survey. To characterize the incidence of epidural hematoma in postoperative spinal patients; to assess the effect of chemical thromboprophylaxis on the risk of epidural hematoma. The precise indications and/or timing of anticoagulation for thromboembolic prophylaxis following spinal surgery are not clear. Patients who endure periods of extended recumbency and limited mobility after major operative spinal interventions may be at increased risk of thromboembolic disease. Among other factors, spine surgeons must weigh the risk of a symptomatic postoperative epidural hematoma against the benefit of DVT/PE prevention when deciding to initiate chemoprophylaxis. However, the incidence of postoperative epidural hematoma is not well-known, leading to uncertainty regarding the real versus perceived risk of this complication. The MEDLINE database was queried using the search terms epidural hematoma and spinal or spine surgery. Abstracts of all identified articles were reviewed. Studies were deemed eligible if they specifically documented the incidence of clinically significant epidural hematoma in a series of patients who underwent spinal surgery. Detailed information from eligible articles was extracted. Data were compiled and analyzed to examine incidences of clinically relevant postoperative epidural hematoma (i.e., resulted in new, associated neurologic deficit). Of 493 abstracts that were identified in the search, a total of sixteen articles were eligible for full review. From this review, the range of reported incidences of epidural hematoma in the literature ranges from 0% to 0.7% in studies where patients received chemical anticoagulation and 0% and 1% in all of the included studies. In no study was the incidence of clinically relevant epidural hematoma greater than 1%. The catastrophic morbidity of a symptomatic postoperative epidural hematoma remains a substantial disincentive to start chemoprophylaxis after spinal surgery. The rarity of this complication makes study of its risk factors difficult. Although many surgeons perceive the risk to be higher, the reported incidences of clinically relevant postoperative epidural hematoma are lower, ranging from 0% to 1%. Despite this finding, there is insufficient published data available to precisely define the safety of postoperative chemoprophylaxis. Though not pertaining to prophylaxis, the available evidence does suggest that use of therapeutic doses of heparin in postoperative spinal patients who sustain a PE may have a higher incidence of bleeding complications.

Bilateral Rectus Sheath Hematoma Developing During Anticoagulant Therapy

A 74-year-old woman presented with severe progressively worsening abdominal pain after defecation. She had been diagnosed as having unstable angina and had been given 100 mg aspirin and started on a therapeutic dose of heparin and nitroglycerin infusion. At the time of presentation, physical examination revealed a painful large mass in the lower abdominal quadrants extending bilaterally, with no skin discoloration. The blood pressure was 80/50 mm Hg, and the pulse rate was 80 bpm while the patient was receiving oral β-blocker therapy. Her hemoglobin dropped from 13.4 to 9.4 g/dL, and the activated partial thromboplastin time was 61.7 seconds. Computed tomography of the abdomen without contrast (Figure 1A) showed a huge bilateral rectus sheath hematoma measuring 15.5×12.5×7.5 cm with a fluid-fluid …

Clinical characteristics and laboratory testing of patients with suspected HIT: A survey on current practice in 11 university hospitals in France

Summary We undertook a survey of French university hospital hematological laboratories to ascertain the clinical characteristics of patients with suspected HIT, the laboratory tests performed, and the therapeutic strategy adopted in current practice. Methods A standardized medical records database for patients with suspected HIT was sent to 19 laboratories. During two months, all consecutive patients for whom a biological test was performed were included. Results 169 patients were included, 27 (16%) patients having a final diagnosis of HIT. At the time HIT was suspected, the heparin duration and the level of thrombocytopenia were similar in HIT- positive and HIT-negative groups. The use of unfractionated heparin, a therapeutic heparin dose regimen and the presence of thrombotic complications were significantly more frequent in HIT-positive patients. When the heparin dose regimen was taken into account, only thrombotic complications under a therapeutic dose regimen were significantly increased in HIT-positive patients. Eighty-six percent of patients presented at least one alternative diagnosis of thrombocytopenia without significant difference between the two groups. Laboratory tests were performed after a mean of 0.3 days and mainly consisted of antigen assays. At the time HIT was suspected, heparin was stopped in 56 (33%) patients, being replaced mainly by danaparoid. Only three laboratories declared they usually received all the necessary clinical information to establish the likelihood of HIT. Conclusion In current practice in France, the clinical probability of HIT is rarely established, leading to systematic requests for laboratory HIT tests.

Anestesi ved keisersnitt

Regional anaesthesia (epidural or spinal anaesthesia) is increasingly used for elective and emergency caesarean sections and is considered to be safer for the mother than general anaesthesia. We present some factors that are important to consider when choosing the anaesthetic method for caesarean section. The article is based on obstetric anaesthesia textbooks, non-systematic searches in PubMed and own clinical experience. When regional anaesthesia is correctly administrated the foetus/neonate and mother are not much affected, adverse effects are very rare and it is possible to establish contact between the mother and newborn immediately after delivery. Spinal anaesthesia is most common. Epidural anaesthesia is most often used in emergency situations when caesarean section has to be performed instead of the expected vaginal delivery and the women has already been given an epidural. Prophylactic epidural access may be prepared during delivery in women with a high risk of complications in general anaesthesia. Combined spinal and epidural anaesthesia is also an option. The most common side effect with regional anaesthesia is hypotension. Recommended preventive measures for hypotension are to cohydrate patients when inducing anaesthesia, to administer small doses of phenylephrine intravenously and to wrap the woman's legs with elastic bandages. There are few contraindications to regional anaesthesia. Women using low-molecular heparin in therapeutic doses or have massive bleeding are not suitable for regional anaesthesia. There are few adverse effects of regional anaesthesia in caesarean section except for hypotension that can be easily treated.

Antithrombosis Trials: Should we test therapeutic heparin adjusted based on activated partial thromboplastin time in septic shock?*

Barochia, Amisha V. MBBS; Li, Yan MD; Cui, Xizhong MD, PhD; Sweeney, Daniel A. MD; Natanson, Charles MD; Eichacker, Peter Q. MD Author Information

Guidelines for the diagnosis and management of disseminated intravascular coagulation

The diagnosis of disseminated intravascular coagulation (DIC) should encompass both clinical and laboratory information. The International Society for Thrombosis and Haemostasis (ISTH) DIC scoring system provides objective measurement of DIC. Where DIC is present the scoring system correlates with key clinical observations and outcomes. It is important to repeat the tests to monitor the dynamically changing scenario based on laboratory results and clinical observations. The cornerstone of the treatment of DIC is treatment of the underlying condition. Transfusion of platelets or plasma (components) in patients with DIC should not primarily be based on laboratory results and should in general be reserved for patients who present with bleeding. In patients with DIC and bleeding or at high risk of bleeding (e.g. postoperative patients or patients due to undergo an invasive procedure) and a platelet count of <50 x 10(9)/l transfusion of platelets should be considered. In non-bleeding patients with DIC, prophylactic platelet transfusion is not given unless it is perceived that there is a high risk of bleeding. In bleeding patients with DIC and prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT), administration of fresh frozen plasma (FFP) may be useful. It should not be instituted based on laboratory tests alone but should be considered in those with active bleeding and in those requiring an invasive procedure. There is no evidence that infusion of plasma stimulates the ongoing activation of coagulation. If transfusion of FFP is not possible in patients with bleeding because of fluid overload, consider using factor concentrates such as prothrombin complex concentrate, recognising that these will only partially correct the defect because they contain only selected factors, whereas in DIC there is a global deficiency of coagulation factors. Severe hypofibrinogenaemia (<1 g/l) that persists despite FFP replacement may be treated with fibrinogen concentrate or cryoprecipitate. In cases of DIC where thrombosis predominates, such as arterial or venous thromboembolism, severe purpura fulminans associated with acral ischemia or vascular skin infarction, therapeutic doses of heparin should be considered. In these patients where there is perceived to be a co-existing high risk of bleeding there may be benefits in using continuous infusion unfractionated heparin (UFH) due to its short half-life and reversibility. Weight adjusted doses (e.g. 10 mu/kg/h) may be used without the intention of prolonging the APTT ratio to 1.5-2.5 times the control. Monitoring the APTT in these cases may be complicated and clinical observation for signs of bleeding is important. In critically ill, non-bleeding patients with DIC, prophylaxis for venous thromboembolism with prophylactic doses of heparin or low molecular weight heparin is recommended. Consider treating patients with severe sepsis and DIC with recombinant human activated protein C (continuous infusion, 24 microg/kg/h for 4 d). Patients at high risk of bleeding should not be given recombinant human activated protein C. Current manufacturers guidance advises against using this product in patients with platelet counts of <30 x 10(9)/l. In the event of invasive procedures, administration of recombinant human activated protein C should be discontinued shortly before the intervention (elimination half-life approximately 20 min) and may be resumed a few hours later, dependent on the clinical situation. In the absence of further prospective evidence from randomised controlled trials confirming a beneficial effect of antithrombin concentrate on clinically relevant endpoints in patients with DIC and not receiving heparin, administration of antithrombin cannot be recommended. In general, patients with DIC should not be treated with antifibrinolytic agents. Patients with DIC that is characterised by a primary hyperfibrinolytic state and who present with severe bleeding could be treated with lysine analogues, such as tranexamic acid (e.g. 1 g every 8 h).

Perioperative anticoagulation in patients having implantation of a cardiac pacemaker or defibrillator: a systematic review and practical management guide.

The perioperative management of anticoagulation in patients who are having implantation of a pacemaker or implantable cardioverter defibrillator (ICD) is a common clinical problem in which best clinical practise is not established. We performed a systematic review of the literature to assess the safety (pocket hematoma risk) and efficacy (thromboembolism risk) of different management strategies. We included studies involving patients who were having pacemaker or ICD implantation whenever a portion of these patients were receiving a coumarin and also assessed pocket hematoma or thromboembolism. We identified eight studies that assessed two strategies used for perioperative anticoagulation management: interruption of a coumarin and use of bridging anticoagulation with a short-acting heparin; and perioperative continuation of a coumarin. A strategy involving bridging anticoagulation with therapeutic-dose heparin was associated with an incidence of pocket hematoma of 12-20%. A strategy involving perioperative continuation of a coumarin was associated with an incidence of pocket bleeding of 1.9-6.6%. The incidence of thromboembolic events was 0-1%, irrespective of the perioperative anticoagulation strategy used. The perioperative anticoagulation management of patients who require pacemaker or ICD implantation is not established but a strategy involving postoperative bridging with intravenous heparin confers a high risk for bleeding whereas perioperative continuation of a coumarin appears to confer a lower risk for bleeding.

Catastrophic antiphospholipid syndrome mimicking a malignant pancreatic tumour – a case report

The catastrophic antiphospholipid syndrome is characterised by rapid onset thromboses, often resistant to conventional anticoagulant treatment, and resulting in life threatening multiple organ dysfunction. The diagnosis of catastrophic antiphospholipid syndrome may be difficult, predominantly due to its frequently atypical presentation. We report a case of a 35-year-old female who presented with a pancreatic tumour and extensive thromboses. Following a storm of ischemic events due to thrombotic occlusions in spite of therapeutic heparin dose, the suspicion of catastrophic antiphospholipid syndrome emerged. The patient was successfully treated with anticoagulants, immunoglobulins, plasmapheresis and rituximab. The present report shows that the use of the diluted Russell's viper venom time can be helpful in providing additional information on the lupus anticoagulants antibody status, allowing careful monitoring of lupus anticoagulants conversion and hence response to therapy.

Gigantic retroperitoneal hematoma as a complication of anticoagulation therapy with heparin in therapeutic doses: a case report

IntroductionSpontaneous retroperitoneal hemorrhage is a distinct clinical entity that can present as a rare life-threatening event characterized by sudden onset of bleeding into the retroperitoneal space, occurring in association with bleeding disorders, intratumoral bleeding, or ruptures of any retroperitoneal organ or aneurysm. The spontaneous form is the most infrequent retroperitoneal hemorrhage, causing significant morbidity and representing a diagnostic challenge.Case presentationWe report the case of a patient with coronary artery disease who presented with transient ischemic attack, in whom anticoagulant therapy with heparin precipitated a massive spontaneous atraumatic retroperitoneal hemorrhage (with international normalized ratio 2.4), which was treated conservatively.ConclusionDelay in diagnosis is potentially fatal and high clinical suspicion remains crucial. Finally, it is a matter of controversy whether retroperitoneal hematomas should be surgically evacuated or conservatively treated and the final decision should be made after taking into consideration patient's general condition and the possibility of permanent femoral or sciatic neuropathy due to compression syndrome.

Stent implantation for the palliative therapy of upper inflow obstruction in bronchial carcinoma

To analyse results obtained in the palliative treatment of obstruction of the upper inflow veins by stent implantation in patients with bronchial carcinoma. Stents were implanted in 14 patients with upper venous obstruction due to bronchial carcinoma (three women, eleven men: mean age 64 [48-74] years), 4 of the superior vena cava (SVC), 6 of the SVC and brachiocephalic vein, 4 of the SVC and subclavian vein. To prevent thromboembolic phenomena all patients received heparin in therapeutic doses for 1-3 days from the time of stents implantation. Treatment was successful (regression of the clinical signs) in 12 of the 14 patients. Six patients died, without recurrence of the clinical signs, an average of 141 (10-420) days after the procedure. Mean survival time of the six patients who remained without symptoms was 3 months (longest interval 9 months). In one patient thrombotic occlusion of the SVC occurred 6 days after stent implantation. However, local thrombolysis successfully re-opened the vessel. Renewed upper vein obstruction occurred in two patients during follow-up. None of the stent filaments fractured and there was no stent dislocation. With a success rate of 86% stent implantation proved to be a sparing procedure in the palliative treatment of upper inflow vein obstruction, especially in patients with extensive malignant disease.

Bilateral Lower Extremity Gangrene Requiring Amputation Associated With Heparin-Induced Thrombocytopenia

Heparin is a common cause of thrombocytopenia in hospitalized patients. Between 10% and 15% of patients receiving therapeutic doses of heparin develop thrombocytopenia. Heparin-induced thrombocytopenia (HIT) can cause severe bleeding and thrombosis owing to intravascular platelet aggregation. HIT must be distinguished from other causes of thrombocytopenia. Importantly, heparin use is often associated with an early fall in the platelet count that usually occurs within the first 4 days of initiation and recovers without cessation of heparin treatment. This nonimmune heparin-associated thrombocytopenia has not been found to be associated with thrombosis and does not necessitate discontinuation of heparin. The authors present a case report of a 70-year-old man who received heparin therapy following aortic tissue valve replacement and aortic root repair with graft and developed bilateral lower extremity arterial clots 6 days postoperatively in the setting of positive heparin antibody titers. Ultimately the patient required bilateral above-knee amputations.

The Incidence and Clinical Features of Heparin-Induced Thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is an important adverse reaction of heparin therapy that can have catastrophic consequences if overlooked or misdiagnosed. Treatment with either unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) can trigger this complication. Orthopedic, cardiac, and vascular surgery patients exposed to prophylactic or therapeutic doses of heparin are at particular risk. Awareness of the clinical features and different presentations of HIT are essential for preventing severe morbidity and mortality associated with this disease.

Accuracy of methods to estimate ionized and “corrected” serum calcium concentrations in critically ill multiple trauma patients receiving specialized nutrition support

The purpose of this study was to determine the accuracy of 22 published methods to estimate serum ionized calcium (iCa) and "corrected" total serum calcium (totCa) concentrations in critically ill, multiple trauma patients. Seven of these formulas estimated iCa and 15 were directed toward predicting a "corrected" totCa. Adult patients admitted to the trauma intensive care unit who received specialized nutrition support were consecutively recruited for study. Patients who received blood products, i.v. calcium, or therapeutic doses of heparin within 24 hours before the laboratory measurements or had a history of cancer, bone disease, parathyroid disease, hyperphosphatemia (> or = 6 mg/dL), hyperbilirubinemia (> 3.5 mg/dL), or renal failure requiring dialysis were excluded. The 22 published methods were analyzed for sensitivity, specificity, percentage false negatives, and percentage false positives for predicting hypocalcemia or hypercalcemia. One hundred patients were studied 4.9 +/- 3.3 days postinjury and were receiving enteral nutrition (n = 81), parenteral nutrition (n = 18), or both (n = 1) at the time of study. Twenty-one patients were hypocalcemic (iCa < or = 1.12 mmol/L) and 6 were hypercalcemic (iCa > or = 1.32 mmol/L). The mean sensitivity of the 22 methods for assessing hypocalcemia was 25% +/- 32% and the specificity was 90% +/- 18%. Although the average percentage of false positives for assessing hypocalcemia was 10% +/- 18%, the mean percentage of false negatives was inordinately high at 75% +/- 32%. The most common method for determination of "corrected" totCa concentration ["corrected" calcium = totCa + (0.8 x (4-serum albumin concentration))] had a sensitivity of only 5%. The McLean-Hastings nomogram method, the most common method for estimating serum iCa concentration, had a sensitivity of 67% but unfortunately also had a significant false-positive rate of 27%. Serum totCa correlated modestly with iCa (r2 = .334, p < .001). Those patients with a serum albumin < or = 2 g/dL (n = 43) had a significantly higher prevalence of hypocalcemia than those with a higher serum albumin concentration (37% incidence of hypocalcemia vs 10%, respectively, p < .002). Aberrations in calcium homeostasis are frequent (27%) in postresuscitative critically ill multiple trauma patients. Methods for predicting hypocalcemia lack sensitivity and are often associated with an unacceptable rate of false negatives. Predictive methods for estimating ionized or corrected serum concentrations should not be used. Direct measurement of serum iCa concentration is indicated for assessing calcium status for this population.

Clinical Suspicion of Fatal Pulmonary Embolism

BackgroundLess than one third of patients with fatal pulmonary embolism (PE) are identified prior to autopsy. ObjectiveTo determine whether the clinical syndromes of acute PE are effective at identifying patients who die of this condition. MethodSeven hundred seventy-eight autopsy reports at the Buffalo General Hospital from 1991 to 1996 inclusive were reviewed. Inpatient medical records of 67 patients who were identified as having PE as the primary or major cause of death then were analyzed. ResultsThirty patients (45% [95% confidence interval, 33 to 57%]) had received a diagnosis of PE prior to death, which was marginally higher than the number previously reported (p < 0.05). The diagnosis of PE was significantly lower (13%; p < 0.01) in patients with COPD or coronary artery disease (33%; p < 0.01). In contrast to the prospective investigation of PE diagnosis data, only a minority of patients (6%) presented with pleuritic pain or hemoptysis, while a significantly larger proportion (24%; p < 0.01) of our patients experienced circulatory collapse. Only 55% were identified as having PE from the following clinical syndromes of PE: isolated dyspnea; pleuritic pain and/or hemoptysis; and circulatory collapse. Among the 30 patients suspected of having PE, only 14 (47%) received IV heparin in therapeutic doses, despite clinical suspicion. ConclusionOur results show a modest increase in the correct antemortem diagnosis of fatal PE. The current clinical syndromes used as markers for suspecting PE are not sufficient to detect patients who ultimately die of PE. Physicians should maintain a higher index of suspicion since fatal PE does not always present as one of the three clinical syndromes of PE. Once PE is suspected, heparin therapy should be started early.

Thromboprophylaxis using a low molecular weight heparin delays fracture repair.

Low molecular weight heparins are significantly superior to unfractionated heparin or warfarin in the prevention of thromboembolic episodes associated with orthopaedic surgery. Therapeutic doses of heparin and warfarin have been shown to delay bone repair in a rabbit model. The current study investigated the effect of prophylactic administration of a low molecular weight heparin, enoxaparin, on the healing of a closed rabbit rib fracture. Fracture healing was assessed using histomorphometric, histologic, and immunohistochemical methods at 3, 7, and 14 days, and biomechanical testing with torsional loading was assessed after 21 days. Bone repair was significantly attenuated at all times in animals receiving subcutaneous enoxaparin compared with that of the control animals. Numerous putative mechanisms for this phenomenon are discussed, and additional studies are proposed to elucidate the effects of this pharmacologically diverse group of compounds on all aspects of bone physiology and repair.

Perioperative Management of Long-Term Anticoagulation

When the need for surgery arises, temporary interruption of long-term anticoagulation exposes patients to additional thrombotic risk. There is no consensus as to how perioperative anticoagulation should be managed in this setting. Based on an individual assessment of risk factors for arterial or venous thromboembolism and the risk of postoperative bleeding, this review outlines an approach to the perioperative management of anticoagulation that is designed to optimize patient safety and efficient delivery of health care. The duration of interruption of oral anticoagulation is minimized by withholding four daily doses of warfarin before surgery, and by restarting warfarin the same day that surgery is performed. This will usually achieve satisfactory coagulation status intraoperatively (e.g., International Normalized Ratio of 1.5 or less) with a low risk of postoperative bleeding. Supplemental prophylaxis with therapeutic doses of heparin, usually unfractionated heparin, can be reserved for patients with the highest risk of thromboembolism. In the preoperative period, this applies to patients who have had an episode of arterial or venous thromboembolism in the preceding month. In the postoperative period, this approach is generally reserved for patients with an episode of venous thromboembolism in the preceding 3 months, and patients with an episode of arterial embolism in the preceding month who have a low risk of bleeding. Differences in the approach to management of anticoagulation before and after surgery relate to the fact that surgery is an important risk factor for venous, but not arterial, thromboembolism, and that recent surgery greatly increases the risk of anticoagulant-induced bleeding. Subcutaneous unfractionated or low-molecular-weight heparin, in doses recommended to prevent venous thromboembolism in high-risk surgical patients, should be administered to in-patients who have a lesser risk of thromboembolism until oral anticoagulation is reestablished.