Continuous Intravenous Infusion Of Heparin Research Articles

A case of pancreatic head cancer with Trousseau’s syndrome treated with radical resection and anticoagulant therapy

BackgroundThe primary disease of Trousseau’s syndrome is often highly advanced cancer, and treatment of the primary disease after cerebral infarction is often difficult. We herein report a case of pancreatic head cancer with Trousseau’s syndrome treated with radical resection and anticoagulant therapy.Case presentationA 78-year-old man was admitted with dizziness and diagnosed with cerebral infarction. Abdominal contrast-enhanced computed tomography for a thorough checkup indicated borderline resectable pancreatic head cancer. Radical resection after neoadjuvant chemotherapy (NAC; gemcitabine plus nab-paclitaxel) was scheduled. During the second course of NAC, multiple cerebral infarctions recurred, and the patient was diagnosed with Trousseau’s syndrome. Continuous intravenous infusion of heparin was started for cerebral infarction. Since it was impossible to continue NAC and there was no worsening of imaging findings, radical resection was planned. Thereafter, he underwent pancreatoduodenectomy with superior mesenteric vein resection. The patient progressed well and was discharged on the 19th day after surgery. He continued subcutaneous injection of heparin at home and is alive without recurrence of cancer or cerebral infarction at more than 21 months after surgery.ConclusionSurgical treatment may be an option for pancreatic cancer with Trousseau’s syndrome under favorable conditions.

Free Jejunal Graft Interposition with Vascular Reconstruction in Patients Undergoing Pharyngo Laryngo Esophagectomy

Pharyngo-esophageal reconstruction using free jejunal grafts has been widely used for the treatment of locally advanced carcinomas of the hypopharynx and cervical esophagus. However, the procedure is technically demanding and requires complex recontractions. The aim of this study was to evaluate our institutional outcomes of reconstruction using a free jejunal graft with vascular reconstruction in patients undergoing pharyngo laryngo esophagectomy with a multidisciplinary surgical team. There were 90 consecutive patients between October 2006 and February 2021. The mean age was 64.6±10.3years, and there were 76 male patients. Of 90 patients, 49 underwent preoperative chemotherapy and/or radiotherapy. Jejunal vessels were commonly anastomosed to the common carotid artery and the internal jugular vein (77.8% and 92.2%, respectively). Continuous intravenous infusion of heparin was used postoperatively. Necrosis of the graft was observed in 5 patients. An isolated revision of vein was necessary in 1 patient. In all cases of graft failure, heparin was not used postoperatively. On the other hand, among the patients without graft failure, heparin was used for about two-thirds of the patients and was significantly different (0% vs. 66%, P=0.01). Free jejunal graft with vessel reconstruction is a safe and effective method for patients undergoing pharyngo laryngo esophagectomy. The position for the prevention of kinking as well anastomosis maneuver of vein is especially important. Moreover, early postoperative anticoagulation is essential.

Recurrent cerebral attack caused by thrombosis in the pulmonary vein stump in a patient with left upper lobectomy on anticoagulant therapy: case report and literature review

BackgroundThrombus formation in the pulmonary vein stump after pulmonary resection has recently been identified as a cause of systemic thrombosis including brain infarction. However, there is limited research focusing on the clinical course of pulmonary vein stump thrombus, and optimal treatment and prevention strategies of this important complication have not been established.Case presentationA 77-year-old woman was diagnosed with lung cancer of the left upper lobe, cT4N2M0, cStage IIIB. As the tumor was considered to be completely resectable, the patient underwent a left upper lobectomy with angioplasty of the left pulmonary artery. The final pathological stage was pT4N2M0, pStage IIIB. The patient developed paralysis of the right upper limb and dysarthria on the 8th postoperative day. Diffusion-weighted magnetic resonance imaging (MRI) of the brain showed multiple high-intensity signals in the area of the left middle cerebral artery, which were not detected on preoperative MRI. She was diagnosed with a cerebral infarction and started on acute-phase treatment including anticoagulation with continuous intravenous heparin infusion. The neurological symptoms improved the following day. Contrast-enhanced chest CT scan revealed thrombus in the left superior pulmonary vein stump measuring 10 mm in diameter. She had no comorbidity related to the cerebral attack. After the treatment was initiated, her symptoms became stable. However, symptoms of altered consciousness, dysarthria, and hemiparesis re-occurred on the 19th postoperative day and improved within an hour. The thrombus in the left superior pulmonary vein stump disappeared on follow-up contrast-enhanced chest CT performed the same day.ConclusionsThis is the first report of recurrent brain attack caused by thrombosis in the pulmonary vein stump in a patient receiving anticoagulant therapy. The present case suggests the possibility of thrombus mobilization causing recurrent systemic thrombosis, and this important complication needs to be considered in future clinical practice.

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Introduction: We report a case of a patient who had a Y-graft replacement after the rupture of abdominal aortic aneurysm (AAA) and developed heparin-induced thrombocytopenia (HIT) with severe consumptive coagulopathy. Case Description: A 67 year-old man was suffering from sudden, severe back pain and was transported to our emergency room. His blood pressure was 104/52 mmHg, heart rate was 90 bpm, alert consciousness with no specific abnormalities during physical examination on arrival. A CT revealed an AAA with a diameter of 90 mm, and hematoma in retroperitoneum suggesting a rupture of AAA. An emergency Y-graft replacement was performed with a blood loss of 12,897 ml during the operation, and then he entered Surgical ICU. Renal replacement therapy was performed on Day 7 for acute kidney injury developed postoperatively. Nafamostat mesilate was administrated as anticoagulant. We found a thrombus in his right internal jugular vein on CT scanned on Day 9, so we started continuous intravenous infusion of heparin as thrombolytic therapy. On the same day, the hemodiafiltration circuit was frequently occuluded by blood clots. The next day, platelets decreased to 74,000 /μL which was a 60% decrease compared to the day before. We considered the possibility of HIT and DIC, and stopped heparin immediately. We then administrated recombinant thrombomodulin (rTM). On Day 11, HIT antibodies were detected in his blood with a strong positive reaction. A clinical diagnosis of HIT was made, and we continuously administered argatroban. However, we had no choice but to decrease the dosage of argatroban and finally stopped it on Day 15 because of prolonged APTT and bleeding tendency. Of course we already stopped administrating rTM. He fell into multiple organ dysfunction syndrome and died on Day 59. Discussion: We think that HIT led to not only hypercoagulability but also consumptive coagulopathy. Fondaparinux could be effective in this case, but its administration is not admitted in Japan. It is necessary to establish a therapy for HIT-associated consumptive coagulopathy.

Strategies in the treatment for intracranial venous sinus thrombosis

Background Cerebral venous sinus thrombosis (CVST) is a special type of cerebrovascular disease with high morbidity and mortality which often has an unpredictable outcome. It is usually misdiagnosed because of different causes and variable clinical manifestations. How to improve the diagnosis and therapy of CVST is always the hotspot in clinic. This article aims to investigate the effective and safe strategies in the treatment for CVST. Methods Clinical data of 52 patients diagnosed with CVST were retrospectively analyzed. These patients were subdivided into mild type and severe type according to the features of symptoms, signs, lumbar puncture pressure and imaging. The patients with mild type were treated with systemic anticoagulant therapy combined with intravenous thrombolysis [continuous intravenous infusion of heparin (12.50-25) × 10 3 U/d for 7-10 d followed by a continuous infusion of urokinase (0.50-0.75) × 106 U/d for 5-7 d]. The patients with severe type were treated with endovascular thrombolysis [injection of urokinase (0.50-1) × 10 6 U, 0.10 × 10 6 U/min via carotid or vertebral artery; or intravenous infusion of urokinase 1 × 106 U/d and heparin 25 × 103 U/d for 5-7 d], and superior sagittal sinus cut-open/intrasinus thrombolysis separately. All the patients took oral warfarin for 6-12 months, and follow-up was performed after operation by the method of magnetic resonance venography (MRV). Results Among the 27 cases of mild type receiving systemic anticoagulant agents and intravenous thrombolysis, 14 were cured; 9 were improved; 4 were ineffective. Among the 22 cases of severe type receiving systemic anticoagulant drugs and endovascular thrombolysis, 18 were cured; 3 were improved; 1 was dead. The left 3 cases with gravis type received superior sagittal sinus cut⁃open/intrasinus thrombolysis and were cured. The period of follow-up was between 6 months and 60 months (the median time was 36 months), and no recurrence happened. Conclusion It was probable to subdivide CVST into mild type and severe type according to the features of symptoms, signs, lumbar puncture pressure and imaging. Different therapeutic strategies were proved to be safe and effective in the treatment of different types.

止血に難渋した慢性DIC患者における抜歯後出血の1例

Disseminated intravascular coagulopathy (DIC) is an acquired bleeding disorder characterized by an imbalance in the hemostatic process, resulting in extensive thrombosis and hemorrhagic complications. DIC exists in both acute and chronic forms. Chronic DIC (compensated DIC) may be associated with subclinical signs and symptoms, and the bleeding disorder may only be identified by laboratory findings. In this paper we report a case of refractory post-extraction hemorrhage compromised by chronic DIC.A 69-year-old man was referred to our hospital because of prolonged bleeding after tooth extraction. The patient had a medical history of large thoracic and abdominal aortic aneurysms. Clinical examination revealed continuous bleeding at the tooth extraction site. Other clinical signs of a hemorrhagic diathesis were not evident. The results of laboratory examinations suggested the possibility of chronic DIC. In this patient, oral bleeding was finally managed by continuous intravenous infusion of heparin. After that, the patient received careful medical and dental follow-up treatment in our hospital and had no further problems.

Transient cortical blindness after spinal surgery as initial presenting sign of hereditary thrombophilia

Sir, Cortical blindness is a rare complication of spine surgery,[1] and is followed by a period of recovery due to resolution of inflammation and edema around the lesion and to the re-activation of partially damaged perilesional tissue.[2,3] Bilateral occipital abnormalities caused by hypotension, ischemia and infarction are associated with poor prognosis. Herein, we report complete recovery of a case with cortical blindness, despite having an ischemic infarct. A 33-year-old female patient who was otherwise healthy underwent uneventful simple discectomy operation. In the immediate postoperative period, she had a syncopal attack and was hypotensive for 5-6 min. After emergency aid, she regained consciousness and complained that she could not see. On neurologic examination, both pupils were isocoric and equally reactive to light and accomodation. There was perception of hand motion. Fundoscopic examination was normal. Cranial magnetic resonance imaging (MRI) revealed hypodense areas involving the occipital lobes bilaterally [Figs. ​[Figs.1,1, ​,2a2a and ​andb].b]. D-dimer test was positive. Deep vein thrombosis in the right popliteal vein was detected ultrasonographically. In spiral computerized tomography (CT) of the thorax scan, there were patchy consolidation areas. Her electrocardiogram showed sinusal tachycardia with an incomplete right bundle-branch block. There were moderate tricuspid insufficiency and mild pulmonary hypertension echocardiographically. She was diagnosed to have massive pulmonary embolism and cortical blindness, and was admitted to the intensive care unit. Treatment was started with continuous intravenous heparin infusion. The patient's vision gradually began to improve within 24 h. Radiological cure with normal thoracal CT was seen on the seventh day. Her vision restored to its preoperative level on the 25th day. After 2 months, there were relative deficits in the right lower temporal quadrant and in the left lower hemifield in visual field examination. Contrast sensitivity evaluation showed losses at high frequencies in the right eye and at all spatial frequencies in the left eye. Color vision assessment revealed low pattern discrimination. For excluding any prothrombotic state, a haemotologic evaluation revealed heterozigousity for factor V Leiden R506Q, protrombin G20210A and MTHFRC677T. Anticoagulant therapy was initiated. In the 3rd year follow-up of the patient, near-complete regression of the infarct area was found in the MRI and improvement of visual field defects was observed [Fig. 3]. Color vision was near-perfect in both eyes. Contrast sensitivity was slightly improved. Figure 1 Diffusion-weighted image showing diffusion restriction compatible with the acute infarct involving the striate and extrastriate cortex (arrows) Figure 2 (a and b) Axial T2-weighted images showing hyperintense areas compatible with the acute infarct involving the striate and extrastriate cortex (arrows) Figure 3 Axial T2-weighted control image showing near-complete regression. There is an encephalomalasic area in the anterior part of the right occipital lobe Visual impairment in cortical blindness is highly variable, and deficits between the hemifields may be different.[4] In our patient, the infarct area was mainly in the cuneus, and corresponding visual field defects were in the lower hemifields. Besides, infarct area comprised both striate and extra-striate visual cortex initially and corresponding abnormalities in color vision and contrast sensitivity recovered with regression of the infarct area. Occipital lobe infarcts were reported to be frequently associated with a prothrombotic state, and were seen more frequently in younger patients and in patients of the female sex.[5] In young patients with cortical blindness, screening for thrombophilia should be made. Because visual loss may be reversible with initiation of immediate anticoagulation therapy, awareness, evaluation and prompt management of this rare complication is critical.

Hypercoagulability Due to Homocystinuria in a Case of Head and Neck Reconstruction Resolved with Combined Systemic Therapy

Sir: We read with great interest an article recently published in Plastic and Reconstructive Surgery about a case of free flap failure in a patient with homocystinuria.1 The authors faced multiple arterial thrombi during toe-to-hand transfer in their young patient. They tried thrombectomy and multiple local infusions of streptokinase and tissue plasminogen activator, but eventually they could not save the flap. We experienced a similar case in a patient operated on for a squamous cell carcinoma of the floor of the mouth. After resection, he was reconstructed with a free anterolateral thigh musculocutaneous flap. Unfortunately, this flap failed due to venous and arterial thromboses. We tried to overcome the problem with arterial infusion of 1000 IU of streptokinase with opened veins and 4000 IU of subcutaneous heparin postoperatively, but we had no success and explained this failure as a technical error. We then decided to perform another anterolateral thigh musculocutaneous flap from the contralateral side. At this stage, multiple arterial thromboses after every anastomosis with the facial, lingual, and superior thyroid arteries presented. Sometimes thrombosis was evident even before anastomosis. Intraoperative Doppler ultrasound of the carotid artery showed normal flow. Due to this unknown hypercoagulable state, we started with empirical systemic therapy: 50 mg of tissue plasminogen activator intravenously, 0.1 μg/kg per minute continuous intravenous infusion of tirofiban (inhibits platelet aggregation) for 12 hours, and 8000 IU/day of continuous intravenous infusion of heparin. Arterial thrombosis resolved in about 10 minutes, and we then successfully performed vessel repair. From the twelfth postoperative hour until the seventh postoperative day, prophylactic intravenous heparin was administered. From the seventh to the fourteenth postoperative day, 2000 IU of subcutaneous heparin was given three times a day. The postoperative course was uneventful, and after 25 days the patient was discharged. A coagulation work-up was positive for elevated serum homocysteine, consistent with moderate homocystinuria. We agree with the authors that hypercoagulability syndromes2–5 should be included in the differential diagnosis of flap loss, and we think that when faced with this problem only an associated systemic therapy with thrombolytic, antiaggregant, and heparin can resolve the problem. Bleeding could be the main disadvantage, so the whole history, examination, and risk-benefit ratio should be taken into consideration. Stefano Spanio di Spilimbergo, M.D., D.M.D. Antonio Rampazzo, M.D. Roberto Squaquara, M.D. Unità Operativa di Chirurgia Maxillo-Facciale Michelangelo Penzo, M.D. Unità Operativa di Cardiologia Ernesto Padula, M.D. Unità Operativa di Chirurgia Maxillo-Facciale Ospedale S. Bortolo Vicenza, Italia

Coumarin skin necrosis: a severe complication of oral anticoagulation

A 39-year-old white female with severe peripheral arterial disease, due to fibromuscular dysplasia, developed coumarin-induced skin necrosis. Owing to recurrent arterial thromboses, including one episode which resulted in left above-knee amputation, phenprocoumon therapy was initiated, at doses of 15, 9 and 3 mg on the first, second and third days of treatment, respectively. This treatment overlapped with a continuous intravenous infusion of heparin that was adjusted to aPTT levels of 1.5 to 2.5 times the normal range. On the third day of treatment she had an international ratio (INR) 4.5 (normal therapeutic range 2–4.5); the protein C level was below 5%. Heparin therapy was then stopped. Twenty-four hours later she developed severe pain of the left thigh, above the site of the amputation, associated with extensive erythema. Another 24 hours later, petechial hemorrhages had developed (Panel A) and were rapidly followed by necrosis (Panel B). Oral anticoagulation was discontinued and

Continuous Intravenous Heparin Infusion Prevents Peri-operative Thromboembolic Events in Bariatric Surgery Patients

The pharmacokinetics of subcutaneous heparin administration in the obese patient are unpredictable. Peak levels are slowly reached and the effects are not rapidly reversible. Low-dose, continuous, intravenous heparin is easily reversed, is more efficacious and is cost-effective. From November 2000 until July 2005, 822 consecutive patients were administered continuous intravenous unfractionated heparin at 400 U/hr (9,600 U/day) starting in the preoperative holding area and maintained until discharge. All clinically significant events were documented. 634 laparoscopic gastric bypass, 10 revisions and 188 Lap-Band procedures were performed. The mean age was 43+/-11 years (15-74) and mean BMI was 45.2+/-7.1 (30-86). There was only one (0.12%) clinically evident thromboembolic event in the entire cohort (after a gastric bypass). Anti-Xa levels and prothrombin time were followed in a group of 40 patients and were found to be normal in all. Bleeding that required transfusion occurred in 1.3% of patients. In 41 patients (5%), heparin therapy was terminated or temporarily held due to need for extensive adhesiolysis or acute drop in hematocrit, with-or-without other evidence of postoperative bleeding. Average estimated blood loss during surgery was 36 cc (5-500 cc). One patient was inadvertently administered excessive doses of heparin due to a pump error without significant sequelae. Continuous low-dose intravenous heparin therapy is associated with an extremely low incidence of thromboembolic events and a low risk for perioperative hemorrhage. Intravenous heparin also has the benefits of being inexpensive and rapidly reversible.

Upper Airway Obstruction Due to Cervical Hematoma after Stellate Ganglion Block -A case report-

An 81 year old man, suffering from sudden sensorineural hearing loss, received stellate ganglion block while receiving a continuous intravenous infusion of heparin. Four hours after stellate ganglion block, he complained of neck pain and swelling. 36 hours later, he developed dyspnea. A plain radiograph and computed tomograph of the neck revealed narrowing of the upper airway. After a tracheostomy, the dyspnea improved. He was discharged without sequelae 19 days later. We recommend that proper compression of the injected site for over 5 minutes is necessary to avoid a hematoma, and careful observation and immediate treatment should be performed when a hematoma occurs.

Interaction between specific fatty acids, GLP-1 and insulin secretion in humans.

Fatty acids affect insulin secretion in vivo, but little is known about the effects of specific fatty acids. Our aim was to investigate differential effects of acutely increased plasma monounsaturated, polyunsaturated and saturated fatty acids on glucose-stimulated insulin secretion in healthy humans. A new experimental protocol was used to increase plasma monounsaturated (MUFA test), polyunsaturated (PUFA test) or saturated (SFA test) non-esterified fatty acids for 2 h by repeated oral fat feeding and continuous intravenous heparin infusion. This was followed by a hyperglycaemic clamp (10 mmol/l) to test insulin secretion in response to a prior plasma NEFA increase. Total plasma NEFA concentrations were increased during the fat tests compared to the control visit (1.7-fold increase for MUFA and SFA tests and 1.4-fold increase for PUFA test; p<0.001). Exaggerated responses in plasma insulin, C-peptide and proinsulin concentrations were seen during the hyperglycaemic clamp after increasing plasma NEFA concentrations compared with the control (p<0.01). The effects were greatest for the MUFA test followed by the PUFA test and SFA test (p<0.01). Plasma GLP-1 concentrations increased during fat feeding, with a higher response during the MUFA test compared to PUFA and SFA tests (p<0.01). Increasing plasma NEFA concentrations by oral fat feeding with heparin infusion augments glucose-stimulated insulin secretion with the greatest effect for monounsaturated fatty acids and the lowest effect for saturated fatty acids. Monounsaturated fatty acids also increase GLP-1 more than saturated fatty acids. Therefore, the exaggerated insulin concentrations could be due to both NEFA and GLP-1.

A Case of Acute Myocardial Infarction In Man Treated with Chemotherapy containing Doxorubicin for Non-Hodgkin Lymphoma.

Anthracyclines have been widely used in cancer therapy due to their efficacy in the treatment of various solid tumors and hematologic malignancy. Cumulative dose-related cardiotoxicity is a well-known toxicity of anthracyclines. Particularly, at total doses of more than 550 mg/m 2 , therapy with anthracyclines can produce irreversible cardiac injury. Anthracycline-induced cardiac toxicity usually manifests by congestive heart failure or arrhythmia. In contrast, acute myocardial infarction is a rare event of anthracycline-induced heart diseases. A 31-year-old man with non-Hodgkin lymphoma (NHL and a single cardiac risk factor, smoking, presented with chest pain after receiving a 2 nd round of CEOP-BLAM chemotherapy. An electrocardiogram revealed ST segment elevation in the inferior leads consistent with acute myocardial infarction. An echocardiogram revealed an ejection fraction of 60% and severe hypokinesia in the inferior wall. Three days later, coronary angiography revealed 50% of luminal stenosis of right coronary artery (RCA and near total occlusion with a large thrombi in the m-RCA. Following balloon angioplasty and stent insertion, the patient was transferred to the coronary care unit and continuous intravenous heparin infusion was started. On the 10th day, the patient was discharged in good condition. Six months later, follow-up coronary angiography showed no significant lesion in the right coronary artery. In a young man with NHL, we report an acute myocardial infarction after a 2nd course of CEOP-BLAM chemotherapy with a review of the relevant literature. (Korean Circulation J 2001;30(5 :507-511

The Economic Impact of Treating Deep Vein Thrombosis with Low-Molecular-Weight Heparin: Outcome of Therapy and Health Economy Aspects

Subcutaneous low-molecular-weight heparin (LMWH) is at least as safe and effective as classical intravenous heparin therapy for the treatment of proximal vein thrombosis. Anticoagulant monitoring and intravenous administration are not required with LMWH treatment, therefore this therapy may offer economic advantages. An economic evaluation of these therapeutic approaches was performed comparing the costs and effectiveness. The evaluation was aimed at helping decision-makers to maximize the health of the population served, subject to available resources. The American-Canadian Thrombosis Study was a multicentre, randomized, double-blind clinical trial that compared treatment by initial continuous intravenous infusion of heparin (followed by 3 months of warfarin therapy) with a once-daily dose of subcutaneous LMWH, tinzaparin sodium (followed by 3 months of warfarin treatment) in patients with acute proximal deep vein thrombosis. In the LMWH-treated group, the cost incurred for 100 patients was $399,403 (Canadian) or $335,687 (US) with a frequency of objectively documented recurrent venous thromboembolism of 2.8%. In the intravenous heparin-treated group, the cost incurred for 100 patients was $414,655 (Canadian) or $375,836 (US), with a frequency of objectively documented recurrent venous thromboembolism of 6.9%. These results show a cost saving of $15,252 (Canadian) or $40,149 (US) with the use of LMWH. Multiple sensitivity analyses did not alter the findings of the study which indicated that LMWH therapy is at least as safe and effective but less costly than intravenous heparin treatment. The potential for outpatient therapy in up to 37% of patients who are receiving LMWH would substantially augment the cost-saving. The cost-effectiveness findings presented in this paper are based on the assumption that all costs are covered by a single payer. Outpatient management in many countries will shift the healthcare costs from the healthcare payer to the patient, increasing the economic burden to the patient.

P13. Depletion of intravascular pools of tissue factor pathway inhibitor (TFPI) during repeated or continuous intravenous infusion of heparin in man

P13. Depletion of intravascular pools of tissue factor pathway inhibitor (TFPI) during repeated or continuous intravenous infusion of heparin in man

Depletion of Intravascular Pools of Tissue Factor Pathway Inhibitor (TFPI) during Repeated or Continuous Intravenous Infusion of Heparin in Man

Tissue factor pathway inhibitor (TFPI) is a potent inhibitor of the extrinsic coagulation system. TFPI is increased several-fold in postheparin plasma and thereby thought to contribute significantly to the antithrombotic action of heparin. The present study was conducted to investigate how repeated (n = 8) and continuous (n = 6) administration of heparin affect plasma TFPI and the inhibition of tissue factor (TF)-induced coagulation ex vivo in humans. Free TFPI antigen (TFPI Ag) increased from 19.2 +/- 4.0 ng/ml to 204.7 +/- 31.7 ng/ml after intravenous injection of 5000 IU of unfractionated heparin. Five repeated injections of 5000 IU of heparin at 4 h intervals caused a progressive decrease (-45 +/- 8%, p < 0.0001 for time effect) in heparin-releasable TFPI and a progressive shortening of the clotting time as determined in a dilute prothrombin time assay (dPT) (-8.7 +/- 6.1 s, p < 0.0001). The basal concentration of TFPI Ag in plasma collected immediately before each heparin injection was decreased by 29 +/- 15% (p < 0.0001), whereas the dPT was decreased by 6.9 +/- 3.5 s (p < 0.0001). During a 24 h continuous infusion of heparin TFPI Ag decreased from 161.5 +/- 26.0 ng/ml to 35.6 +/- 4.7 ng/ml (-77.3 +/- 5.1%) (p < 0.0001). The contribution of TFPI to the inhibition of TF-induced coagulation during heparin infusion was estimated to decrease from 60 +/- 15% to 20 +/- 10% (p < 0.0001). The present data indicate partial depletion of intravascular pools of TFPI by repeated and continuous heparin administration and thereby attenuation of its contribution to the antithrombotic action of heparin.

Vascular catheter-related bloodstream infection due to Acinetobacter johnsonii (formerly Acinetobacter calcoaceticus var. lwoffi): report of 13 cases.

Although Acinetobacter baumannii (formerly Acinetobacter calcoaceticus var. anitratus) is known to be an important nosocomial pathogen, the clinical impact of other Acinetobacter species is not fully understood. Acinetobacter johnsonii (formerly a subset of A. calcoaceticus var. lwoffii) is considered a commensal on human skin, and infections due to this organism have not been reported previously. During a study period of 18 months, however, 13 patients at 6 hospitals developed catheter-related bloodstream infections caused by A. johnsonii. All patients had an indwelling peripheral or central venous catheter, and 11 patients were receiving a continuous intravenous infusion of heparin via the offending catheter. The clinical course of A. johnsonii bacteremia was usually benign. Infections responded readily to removal of the catheter, with or without administration of appropriate antibiotics. No insertion-site infections were documented. Thus A. johnsonii must be regarded as an organism that can cause rare cases of bloodstream infection in immunocompetent patients.

Persistent generation of thrombin after acute myocardial infarction.

During the acute phase of myocardial infarction, the generation of thrombin is reflected in the sudden rise of fibrinopeptide A (FPA) and the thrombin-antithrombin III (TAT) complex in blood. We have systematically determined the FPA and TAT plasma concentrations over a period of 14 days after acute myocardial infarction in 100 patients. Mean levels of both thrombin markers were the highest on admission, remained elevated over the following few days, and then gradually declined after day 5. Still, by the end of the first week two thirds of the patients had distinctly elevated TAT and FPA levels, and by the end of the second week such an abnormality was present in half of them. Continuous intravenous heparin infusion at a dose of 20,000 units/day, administered for 1 week to patients who had either received (n = 21) or not received (n = 17) streptokinase, led to a significant depression (p less than 0.05) of thrombin markers over the first 48 hours, an effect that did not persist over the subsequent days of treatment. In patients not assigned to heparin treatment, those in heart failure had significantly (p less than 0.05) higher mean TAT and FPA values on days 3, 5, and 7 compared with patients in whom heart failure was absent. Infarct extension, pulmonary embolism, and death were also associated with a rise in one or both thrombin markers, often preceding the onset of clinical symptoms. Thrombinogenesis was not accompanied by changes in mean plasma concentrations of prothrombin, antithrombin III, or alpha 2-macroglobulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of controlled adventitial heparin delivery on smooth muscle cell proliferation following endothelial injury.

Continuous intravenous infusion of heparin suppresses smooth muscle cell proliferation in rats after endothelial injury but may lead to hemorrhage and other complications. The anticoagulant property has been removed from chemically modified heparin without loss of antiproliferative effect but use of such compounds is still limited. In this study ethylene-vinyl acetate copolymer matrices containing standard and modified heparin were placed adjacent to rat carotid arteries at the time of balloon dendothelialization. After 14 days arterial occlusion by smooth muscle cell proliferation was defined. Matrix delivery of both heparin compounds effectively diminished this proliferation in comparison to controls without producing systemic anticoagulation or side effects. In addition, this mode of therapy appeared more effective than the administration of the same agents by either intravenous pumps or heparin/polymer matrices placed in a subcutaneous site distant from the injured carotid artery. Thus, heparin's inhibition of smooth muscle cell proliferation after vascular injury might be most effective within the microenvironment of the injured vessel wall, and the accelerated atherosclerosis or restenosis that often follows angioplasty and other vascular interventions might best be treated with site-specific therapy.

Intracranial Hemorrhage after Use of Tissue Plasminogen Activator for Coronary Thrombolysis

Tissue plasminogen activator (tPA), an approved coronary thrombolytic agent, can cause serious bleeding. We report the cases of six patients with intracranial hemorrhage after tPA treatment for acute myocardial infarction. None of the patients were hypertensive at admission, and only one was hypertensive during therapy. Intravenous tPA, 100 mg, was followed by continuous intravenous heparin infusion; intracranial hemorrhage occurred between 2 and 14 hours after tPA infusion ended and between 3 and 17 hours after heparin therapy was started. The partial thromboplastin time (PTT) was excessively prolonged (from 81 s to more than 150 s) in all patients at onset of intracranial hemorrhage. The intracerebral hematomas were predominantly of lobar location, and two patients had multiple simultaneous hemorrhages. Four patients died from massive intracranial hemorrhage; the mechanism for these hemorrhages was unclear. Factors possibly related to hemorrhage include a systemic fibrinolytic state or a platelet anti-aggregant effect produced by tPA and enhanced hemorrhagic tendency caused by the combined effects of tPA and heparin. Local vascular changes at the bleeding site remain as potential contributing factors for isolated intracranial hemorrhage.