Greater Risk Of Bleeding Research Articles

Venous thromboembolism in radical prostatectomy: is heparinoid prophylaxis warranted?

To review the incidence of venous thromboembolism (VTE) after radical retropubic prostatectomy (RRP) and evaluate the need for heparinoid prophylaxis as opposed to mechanical compression devices after RRP. RRP is classified as a category 1 (high risk) procedure for VTE by the American College of Chest Physicians and several international guidelines recommend subcutaneous heparinoids as the preferred prophylaxis. However, this regimen may be associated with a greater risk of bleeding. We have not used heparinoid prophylaxis but place a mechanical compression device for prophylaxis of VTE, and report our clinical experience over a 12-year period. Between 1992 and 2004, all RRPs carried out by one surgeon (M.S.S.) at our centre were retrospectively reviewed after obtaining institutional review board approval. The protocol for prophylaxis of VTE consisted of compression stockings and a sequential compression device from the time of entry into the operating room until complete ambulation (we encourage early ambulation). Patients were evaluated for VTE if they developed any clinical signs or symptoms. Patients were followed at 7 days, 6 weeks and 3 months after RRP in the first year and 6-monthly thereafter. All relevant clinical data and complications were entered in a database. In all there were 1364 RRPs; the mean (sd) age of the patients was 61 (7) years and the mean follow-up 44 (38) months. All patients had a mechanical compression device and ambulated on the first day after surgery. None received heparinoid prophylaxis. Three VTE events were identified (0.21%); two patients had a lower limb VTE and one an upper limb VTE. All were successfully treated with anticoagulation. No patient had a documented pulmonary embolus and none died from VTE. There was one death after RRP, from myocardial infarction. The incidence of VTE after RRP is low, possibly related to the use of a mechanical compression device and early aggressive mobilization. Despite the recommendations by some, we feel that routine heparinoid prophylaxis is questionable.

Neonatal Hemodialysis and Continuous Renal Replacement Therapy

After completing this article, readers should be able to: 1. Describe catheters, dialyzers, and blood lines in hemodialysis for neonates. 2. Explain the blood prime and hemodialysis prescription in hemodialysis for neonates. 3. List potential complications of hemodialysis for neonates. 4. Identify the types of continuous renal replacement therapy (CRRT) in neonates. 5. Explain the dialysis prescription and anticoagulation options for CRRT in neonates. 6. List potential complications of CRRT in neonates. Since the mid-1980s, when dialysis manufacturers began making dialyzers and blood circuit paths that required smaller extracorporeal volumes, hemodialysis has been used successfully to manage renal failure in neonates and infants. Compared with peritoneal dialysis (PD), which is analogous to the “family sedan” in the world of dialysis (slower, more predictable, easier to operate), hemodialysis is the “race car.” Hemodialysis is capable of removing fluids and solutes much more rapidly than is PD. Unlike PD, hemodialysis uses catheters that access the intravascular space directly. Despite the advantages of hemodialysis, the process in neonates is technically more challenging than PD due to the very attributes that make it so effective. Rapid removal of intravascular fluids, exceeding the rate of refill from the extravascular space, causes problems with hypotension due to direct reduction in intravascular volume. Similarly, rapid rates of solute clearance can cause problems with increased intracranial pressure. Catheter placement and maintenance of catheter function can constitute a significant obstacle to hemodialysis. Hemofiltration is very similar to hemodialysis in that patient blood is circulated through an artificial kidney. However, hemofiltration differs from hemodialysis in three significant aspects. First, the hemofilter has larger pore sizes than the standard dialyzer, which allows for excellent fluid removal, even with low blood flow rates, and better larger molecule clearance. Second, hemofiltration runs continuously without the continuous presence of a dialysis nurse. Third, typical hemofiltration uses a pre- or postdilution …

Anticoagulation and platelet antiaggregation therapy in stroke prevention

Purpose of review The results of recent large clinical trials have modified treatment plans formerly based on inferred mechanisms of ischemic stroke and hazards of certain forms of therapy. Recent findings Strong data have emerged to support anticoagulation with warfarin for stroke associated with inferred embolism in a setting of atrial fibrillation. No clear advantage for warfarin over aspirin exists for ischemic stroke in a setting of intracranial atheroma, patent cardiac foramen ovale, or elevated levels of antiphospholipid antibody. Among antiplatelet agents, aspirin and clopidogrel have a similar recurrent stroke risk. Combination therapies with aspirin and warfarin show no additional benefits with regard to stroke prevention and carry higher risks of hemorrhage. Treatment with aspirin combined with specially formulated long-acting dipyridamole carries a lower risk of stroke than aspirin alone and does not increase the risk of hemorrhage significantly. The combination of aspirin and clopidogrel does not reduce the risk of stroke over clopidogrel alone and carries a greater risk of bleeding than clopidogrel alone. Summary Choice of antithrombotic therapy depends on the etiology of the stroke. Oral anticoagulation treatment is the preferred choice for inferred cardioembolism in the setting of atrial fibrillation, while the varying rates of hemorrhage with oral anticoagulants continue to favor antiplatelet therapy in other settings of inferred etiology. Combinations of antithrombotic therapy vary in their lowering of stroke rate, and some raise the risk of hemorrhage. Insufficient data exist to determine whether antithrombotic therapy combined with antihypertensives, statins or other agents will further reduce the risk of stroke in synergistic or supplemental fashion, or give no additional benefit.

Heparin Anticoagulation and Natural Reversal in a Patient with Anaphylactoid Shock to Protamine: A case report

Protamine is the only agent approved to reverse heparin induced anticoagulation after cardiopulmonary bypass, although it may cause systemic hypotension, anaphylaxis or an anaphylactoid reaction, or pulmonary hypertension. However, there are no clinically available alternatives to protamine to neutralize systemic heparin in patients who are known to be allergic to protamine. We anesthetized a patient for mitral valve replacement who had previously an anaphylactoid shock to protamine. Because of the risk of an anaphylactoid shock, we allowed spontaneous reversal of heparin anticoagulation without the use of protamine after cardiopulmonary bypass and achieved a successful result. If a severe adverse reaction to protamine is suspected, it might be appropriate to allow the spontaneous reversal of heparin despite a greater risk of bleeding.

Safety and risk stratification of percutaneous biopsies of adult-sized renal allografts in infant and older pediatric recipients.

Allograft biopsies are the gold standard for evaluating renal graft dysfunction. Adult-sized kidney (ASK) allografts are placed extraperitoneally in older children and adults and transperitoneally in infant recipients. Transperitoneal graft biopsies may be accompanied by a greater risk of bleeding and bowel injury, although no standardized pediatric study of procedure risk relating to transplant placement exists. A retrospective single-center study of 328 consecutive ASK biopsies (277 extraperitoneal and 51 transperitoneal) performed since 1995 was conducted to stringently categorize all identified biopsy procedure complications (bleeding, transfusion requirement, bowel perforation, surgical intervention, and graft loss) relating to allograft placement, surveillance versus protocol biopsies, recipient age, and biopsy needle use, with risk stratification and recommendations for improving procedure safety. Two distinct methods of real-time ultrasound guidance were used. The overall incidence of all adverse effects was 16.1%, with perinephric hematomas accounting for 13.4% and gross hematuria accounting for 2.7%. Hematomas less than 1 cm accounted for 81.4% of all hematomas. Complications of transperitoneal biopsies (using a modified patient placement approach) paralleled those seen in extraperitoneally placed allografts (15.7% vs. 15.5%, P=0.976). Hematomas occurred more frequently (17.8% vs. 8.3%, P=0.010) in clinically indicated versus surveillance biopsies and with 16- versus 18-gauge biopsy needle use (43% vs. 13.3%, P=0.19). Pediatric allograft ASK biopsies can be performed with minimal adverse outcomes. Transperitoneal ASK placement is not a contraindication for percutaneous biopsy. Strategies to improve biopsy safety include recommendations for patient positioning for transperitoneal ASKs, improved techniques for real-time ultrasound guidance, and use of finer gauge needles.

Propranolol plus placebo versus propranolol plus isosorbide-5-mononitrate in the prevention of a first variceal bleed: A double-blind RCT

Nonselective β-blockers are very effective in preventing first variceal bleeding in patients with cirrhosis. Treatment with isosorbide-5-mononitrate (IS-MN) plus propranolol achieves a greater reduction in portal pressure than propranolol alone. The present multicenter, prospective, double-blind, randomized, controlled trial evaluated whether combined drug therapy could be more effective than propranolol alone in preventing variceal bleeding. A total of 349 consecutive cirrhotic patients with gastroesophageal varices were randomized to receive propranolol + placebo (n = 174) or propranolol + IS-MN (n = 175). There were no significant differences in the 1- and 2-year actuarial probability of variceal bleeding between the 2 groups (propranolol + placebo, 8.3% and 10.6%; propranolol + IS-MN, 5% and 12.5%). The only independent predictor of variceal bleeding was a variceal size greater than 5 mm. However, among patients with varices greater than 5 mm (n = 196), there were no significant differences in the incidence of variceal bleeding between the 2 groups. Survival was also similar. Adverse effects were significantly more frequent in the propranolol + IS-MN group due to a greater incidence of headache. There were no significant differences in the incidence of new-onset or worsening ascites or in impairment of renal function. In conclusion, propranolol effectively prevents variceal bleeding. Adding IS-MN does not further decrease the low residual risk of bleeding in patients receiving propranolol. However, the long-term use of this combination drug therapy is safe and may be an alternative in clinical conditions associated with a greater risk of bleeding. (H epatology 2003;37:1260-1266.)

Laparoscopic left hemicolectomy in a patient with cirrhosis scheduled for liver transplantation

Hepatic cirrhosis is a negative prognostic factor for major abdominal surgery, with a greater risk of bleeding, infection, and ascites. The case of a 54-year-man with adenocarcinoma of the sigma affected by hepatitis B virus and hepatitis C virus hepatopathy as well as micro- and macrconodular cirrhosis (Child's B7 stage) waiting for liver transplantation is reported. After a consultation with the liver transplantation our hospital, and considering the the patient's age laparoscopy was determined to be the procedure of choice because it would give him the possibility of a transplantation in the future. A typical left hemicolectomy with left flexure mobilization and mechanic colorectal T-T-anastomosis was therefore performed. All surgical maneuvers in the right hypochondrium were avoided. Mobilization was performed using an ultrasonic scalpel to reduce the risk of bleeding, and the anatomic stump was pulled out by means of a midline minilaparotomy, sparing the anastomotic circles of the abdominal wall. Follow-up evaluation was uneventful. At an 8-month follow-up visit, the patient was in good general condition. In this case, laparoscopic surgery allowed an oncologically suitable colonic resection without complication and poor surgical stress. Moreover, open surgery would have reduced the possibility of a transplantation in the future.

Cerebrovascular complications of alcohol and sympathomimetic drug abuse.

Alcohol abuse has been linked to intracranial hemorrhage, both intracerebral and subarachnoid. Some studies have found a dose-response relationship, so that increasing levels of abuse are associated with greater risk of hemorrhage. However, alcohol abuse has not been clearly linked to cerebral infarction, and some studies find that mild-to-moderate drinking appears to be associated with a decreased risk of cerebral infarction. Intravenous administration of drugs of abuse predisposes to endocarditis, which may lead to embolic stroke. Associations have been reported between various sympathomimetic drugs and cerebral infarction. A possible mechanism for cerebral infarction is focal arterial vasoconstriction and occasionally cerebral vasculitis. Associations have also been reported between various sympathomimetic drugs and intracranial hemorrhage. A likely mechanism for intracranial hemorrhage is acute arterial hypertension. With the exception of endocarditis, management of stroke related to drug abuse is largely supportive, with emphasis on supportive care to prevent stroke complications, physical and occupational therapy, and aggressive addiction rehabilitation.

Safety assessment of drotrecogin alfa (activated) in the treatment of adult patients with severe sepsis.

Drotrecogin alfa (activated; recombinant activated protein C) was shown to reduce 28-day all-cause mortality in patients with severe sepsis and to have an acceptable safety profile in 1690 patients studied in the F1K-MC-EVAD (PROWESS) trial. We analyzed all available data on the safety of treatment with drotrecogin alfa (activated) in 2786 adult patients with severe sepsis enrolled in all phase 2 and 3 clinical trials, and in an estimated 3991 patients receiving the drug in commercial use. Mortality and safety analyses were performed on all available data from adult severe sepsis patients enrolled in seven clinical trials as of 12 April 2002. Trial-specific safety data and spontaneously reported serious adverse events from commercial use were extracted from a pharmacovigilance database. The 28-day mortality rate for all adult patients who received active treatment in all clinical trials was 25.3% (704/2786). Serious bleeding events during the infusion period and 28-day study period occurred in 2.8% (79/2786) and 5.3% (148/2786) of patients, respectively. Of bleeding events during the infusion period, 43% (34/79) were procedure-related. Fatal serious bleeding events during the infusion period occurred in 0.4% (12/2786) of cases. Intracranial hemorrhage (ICH) events during the infusion period and 28-day study period occurred in 0.6% (16/2786) and 1.1% (32/2786) of patients, respectively. Ten out of the 16 ICH events occurring during the study drug infusion period were associated with severe thrombocytopenia (<or= 30000/mm3) and/or meningitis. Serious bleeding and ICH events spontaneously reported from commercial use (n = 3991) occurred in 0.9% and 0.2% of patients, respectively. Drotrecogin alfa (activated) significantly reduces mortality in severe sepsis. The efficacy and safety profiles of drotrecogin alfa (activated) have remained consistent over the conduct of multiple clinical trials. The most important serious adverse event associated with drotrecogin alfa (activated) treatment is bleeding. Additional clinical experience indicates that invasive procedures are associated with a substantial percentage of serious bleeding events, particularly those occurring at the start of infusion of the drug. Severe thrombocytopenia (for all serious bleeding events, including ICH) and meningitis (for ICH only) may be risk factors for serious bleeding. However, patients with severe thrombocytopenia and/or meningitis may be at greater risk for bleeding or ICH in the absence of drug therapy.

Multiplicity of dural arteriovenous fistulas

Dural arteriovenous fistulas (AVFs) are a well-known pathoanatomical and clinical entity. Excluding bilateral involvement of the cavernous sinus, multiple dural AVFs are rare, with isolated reports in the literature. The additional risk associated with multiplicity is unknown, although it has been claimed that there is a greater risk of hemorrhage at presentation. In a group of 284 patients with dural AVFs consecutively treated at a single center, the occurrence of multiplicity is investigated and its risk factors for hemorrhage are identified. Among the 284 patients with both cranial and spinal dural AVFs, 20 patients with multiple fistulas were found. Nineteen (8.1%) of 235 patients with cranial AVFs had multiple cranial fistulas, and one (2%) of 49 patients with spinal AVFs harbored two spinal fistulas. Twelve patients were found to have a lesion at two separate sites, seven patients had them at three locations, and one patient had four fistulas, each at a different site. In the subgroup with multiple AVFs the percentage of hemorrhage at presentation was three times higher than in the entire group (p = 0.01). Cortical venous drainage in cranial fistulas was present in 84% of patients with multiple lesions compared with 46% of patients with solitary lesions (p < 0.005). Multiple dural AVFs are not rare. In this group of 284 patients it was found in 8.1% of all patients with cranial dural AVFs. Multiplicity was associated with a higher percentage of cortical venous drainage, a pattern of drainage reportedly yielding a higher risk for hemorrhage.

Vaginal bleeding in postmenopausal women taking low-dose norethindrone acetate and ethinyl estradiol combinations

Objective: To determine the effect of continuous combined treatment with norethindrone acetate and ethinyl estradiol (E2) on vaginal bleeding, spotting, or bleeding and/or spotting in postmenopausal women. Methods: Two randomized clinical trials were conducted in which participants recorded information on the daily occurrence of vaginal bleeding or spotting. In study 1, 219 postmenopausal women reporting at least ten hot flushes per week were randomized to placebo or one of four treatment groups (0.2 mg norethindrone acetate/1 μg ethinyl E2, 0.5 mg norethindrone acetate/2.5 μg ethinyl E2, 1 mg norethindrone acetate/5 μg ethinyl E2, or 1 mg norethindrone acetate/10 μg ethinyl E2). In study 2, 266 postmenopausal women reporting at least 56 moderate to severe hot flushes were randomized to placebo or one of three treatment groups (0.5 mg norethindrone acetate/2.5 μg ethinyl E2, 1 mg norethindrone acetate/5 μg ethinyl E2, or 1 mg norethindrone acetate/10 μg ethinyl E2). The total duration of treatment was 16 weeks in study 1 and 12 weeks in study 2. In both studies, subjects reported in daily diaries whether they had either bleeding or spotting. Results: In study 1, there was a significantly greater relative risk (RR) for bleeding in the group receiving 1 mg norethindrone acetate/10 μg ethinyl E2 at study weeks 4 and 8 (RR = 1.36 and 95% confidence interval [CI] 1.01, 1.83; RR = 1.37 and 95% CI 1.1, 1.72; respectively) compared with placebo, but not at study weeks 12 or 16. The group receiving 1 mg norethindrone acetate/5 μg ethinyl E2 also had a significantly greater risk at weeks 4 and 8 (RR = 1.5 and 95% CI 1.15, 1.96; RR = 1.33 and 95% CI 1.00, 1.77; respectively), whereas the other dose combinations did not differ from placebo. Results from study 2 were similar to those of study 1. Conclusion: Although there was a greater risk for bleeding and/or spotting at the higher doses of norethindrone acetate and ethinyl E2, this risk declined over time. If compliance with hormone replacement therapy regimens is influenced at least in part by vaginal bleeding, the combined norethindrone acetate/ethinyl E2 regimen investigated in these studies may provide a treatment option.

Aspirin does not increase allogeneic blood transfusion in reoperative coronary artery surgery.

While preoperative aspirin (ASA) therapy does not increase allogeneic transfusion in elective primary coronary artery bypass grafting (CABG) operations, the impact of ASA consumption on transfusion in cardiac operations with greater risk of bleeding has not been investigated. We examined the influence of ASA consumption on mediastinal drainage and allogenic transfusion in 317 patients undergoing reoperative CABG surgery. Patients receiving ASA or ASA containing medications within 7 days preoperatively (n = 215) had similar perioperative characteristics but were older and had smaller red cell volumes than control patients not receiving ASA (n = 102). All patients received aminocaproic acid, but autotransfusion of mediastinal blood or platelet rich plasma, aprotinin, or desmopressin were not used. No significant differences were observed between ASA and control groups with respect to postoperative hematocrit, mediastinal drainage, frequency of reexploration for excessive bleeding, amount of allogeneic packed red blood cell, fresh frozen plasma, platelet concentrate or cryoprecipitate transfusion, or the fraction of patients receiving any allogeneic blood product. There was no difference in mediastinal drainage when stratified by timing of most recent ASA ingestion. Multiple linear regression identified duration of cardiopulmonary bypass (CPB), internal mammary artery harvesting, chronic preoperative steroid therapy and use of an intraaortic balloon pump (IABP) as significant predictors of mediastinal drainage. Logistic regression demonstrated that female gender, prolonged duration of CPB, advanced age, use of IABP, and a negative history of smoking were significant independent predictors of blood product transfusion. There was no significant interaction of preoperative heparin therapy with ASA on transfusion demonstrated by univariate or multivariate analyses. These results indicate that preoperative ASA ingestion is not an important determinant of mediastinal drainage or allogeneic transfusion, even after repeat CABG operations, and that surgical and patient characteristics are more important predictors of these outcomes.

Aspirin Does Not Increase Allogeneic Blood Transfusion in Reoperative Coronary Artery Surgery

While preoperative aspirin (ASA) therapy does not increase allogeneic transfusion in elective primary coronary artery bypass grafting (CABG) operations, the impact of ASA consumption on transfusion in cardiac operations with greater risk of bleeding has not been investigated.We examined the influence of ASA consumption on mediastinal drainage and allogeneic transfusion in 317 patients undergoing reoperative CABG surgery. Patients receiving ASA or ASA containing medications within 7 days preoperatively (n = 215) had similar perioperative characteristics but were older and had smaller red cell volumes than control patients not receiving ASA (n = 102). All patients received aminocaproic acid, but autotransfusion of mediastinal blood or platelet rich plasma, aprotinin, or desmopressin were not used. No significant differences were observed between ASA and control groups with respect to postoperative hematocrit, mediastinal drainage, frequency of reexploration for excessive bleeding, amount of allogeneic packed red blood cell, fresh frozen plasma, platelet concentrate or cryoprecipitate transfusion, or the fraction of patients receiving any allogeneic blood product. There was no difference in mediastinal drainage when stratified by timing of most recent ASA ingestion. Multiple linear regression identified duration of cardiopulmonary bypass (CPB), internal mammary artery harvesting, chronic preoperative steroid therapy and use of an intraaortic balloon pump (IABP) as significant predictors of mediastinal drainage. Logistic regression demonstrated that female gender, prolonged duration of CPB, advanced age, use of IABP, and a negative history of smoking were significant independent predictors of blood product transfusion. There was no significant interaction of preoperative heparin therapy with ASA on transfusion demonstrated by univariate or multivariate analyses. These results indicate that preoperative ASA ingestion is not an important determinant of mediastinal drainage or allogeneic transfusion, even after repeat CABG operations, and that surgical and patient characteristics are more important predictors of these outcomes. (Anesth Analg 1996;83:1178-84)

The Use of a Uterine Tourniquet in the Surgical Management of a Cornual Ectopic Pregnancy

ABSTRACT The surgical management of cornual ectopic pregnancies carries a greater risk of hemorrhage than management of other tubal pregnancies. Wedge resection and hysterectomy are still accepted treatment modalities. We present a case of a cornual pregnancy following in vitro fertilization in which a uterine tourniquet and vasopressin, similar to that used in myomectomies, was used to help promote a bloodless procedure. In the treatment of cornual ectopic pregnancies, a uterine tourniquet in addition to vasopressin may allow for more conservative surgical procedures, with decreased blood loss. (J GYNECOL SURG 11:53, 1995)

Assessment of clinical impact and predisposing factors for neonatal thrombocytopenia.

Thrombocytopenia is a common hemostatic abnormality in the newborn infant. The early diagnosis of thrombocytopenia and the underlying primary pathology process play an important role in reducing the risk of severe complications and mortality. We performed a 2-year prospective study of 643 neonates admitted to our neonatology unit to determine the frequency, predisposing factors, and clinical impact of thrombocytopenia. Thrombocytopenia developed in 18.2% of the preterm neonates and 0.8% of the term neonates. Prematurity, sepsis, hypoxia, intrauterine growth retardation, and disseminated intravascular coagulation were identified as predisposing factors for thrombocytopenia. The incidence of complications and mortality were higher in thrombocytopenic infants. Especially the prognosis was worse in cases who had mucosal hemorrhage, without a relation with the degree of thrombocytopenia. The thrombocytopenia occurred by day 2 in 43% of the infants, and resolved by day 8 in 61%. The platelet count nadir occurred by day 2. Since thrombocytopenic infants are at greater risk for bleeding, and the thrombocytopenia itself may have contributed to the high mortality, predisposing factors such as prematurity, infections, hypoxia must be eliminated by providing better care, giving adequate hygiene of both mother and the baby during the prenatal, natal, and neonatal period.

Complications of percutaneous liver biopsy in children

To determine the frequency and nature of complications after liver biopsy and whether risk factors could be identified to predict these complications, the medical records of all patients (age, 1 week to 28 years) who underwent a percutaneous liver biopsy at Children's Hospital over a 6-year period (1981–1986) were reviewed. Data were collected from 469 (97%) of 483 eligible charts. Twenty-one patients (4.5%) experienced major complications including bile leak (n = 3, 0.6%), prolonged drainage of ascitic fluid (n = 1, 0.2%), pneumothorax (n = 1, 0.2%), bleeding requiring transfusion (n = 13, 2.8%), and death (n = 3, 0.6%). A subgroup of patients (n = 37) with cancer or bone marrow transplantation was found to be at a nearly fivefold greater risk for transfusion than patients with other diagnoses (P = 0.02). All three deaths in previously stable patients occurred in this same high-risk group of patients with cancer or bone marrow transplantation (P < 0.001). Two deaths resulted from disseminated intravascular coagulation and one from bleeding. Diagnosis, age, number of percutaneous passes, and prebiopsy coagulation studies were not predictive of subsequent complications. It is concluded that bleeding that requires transfusion is the most common liver biopsy complication and that it occurs more frequently in children than previously reported. Children with cancer or those who have undergone bone marrow transplantation are at a greater risk for bleeding and death following percutaneous liver biopsy.

Clinical impact of neonatal thrombocytopenia

In a 1-year prospective study, the outcome in infants with a platelet count less than 100 X 10(9)/L (n = 97) was compared with the outcome in an age-, weight-, and disease-matched nonthrombocytopenic control group (n = 80). The hemostatic impact of the thrombocytopenia was assessed by modified template bleeding time, hemorrhage score, and determination of the presence and extent of intraventricular hemorrhage (IVH) in thrombocytopenic infants weighing less than 1500 at birth (n = 39) compared with all nonthrombocytopenic infants less than 1500 g (n = 122) admitted during the study period. The development outcome in infants less than 1500 g was compared at 12 months after delivery. Neonatal thrombocytopenia had a major impact on hemostatic integrity: bleeding time was inversely related to platelet count (r = -0.56, P less than 0.001) and became prolonged when the platelet count fell to less than 100 X 10(9)/L. In addition, many infants (40%) had evidence of platelet dysfunction with prolonged bleeding times despite only moderately reduced platelet counts (75 to 150 X 10(9)/L). The hemorrhage score was greater in the thrombocytopenic infants compared with the sick control infants, and increased as the platelet count fell (r = -0.58, P less than 0.001). The incidence of IVH in thrombocytopenic infants less than 1500 g was 78%, compared with 48% in the nonthrombocytopenic infants (P less than 0.01). In addition, the more severe grades of IVH were more frequent in the thrombocytopenic infants. The serious neurologic morbidity for the surviving infants less than 1500 g was 41% in the thrombocytopenic infants and 7% in the nonthrombocytopenic infants. Thus, on the basis of three indices of abnormal bleeding, thrombocytopenic infants are at greater risk for bleeding than equally sick nonthrombocytopenic infants. The thrombocytopenia itself may have contributed to the high mortality and neurologic morbidity.

Heparin: Do We Understand Its Antithrombotic Actions?

Heparin: Do We Understand Its Antithrombotic Actions?

Anticoagulation therapy in children with mechanical prosthetic cardiac valves

From 1980 through 1984, 28 children younger than 19 years (mean 7.9) underwent cardiac valve replacement with 30 mechanical prostheses. Patients were followed for a total of 471 months (mean 15.7) and received either warfarin (mean 0.16 mg/kg/day) or acetylsalicylic acid and dipyridamole (mean 6.1 and 1.9 mg/kg/day, respectively) as thromboembolism prophylaxis. The frequency and incidence of thromboembolism and hemorrhage were compared. Warfarin-treated patients were at increased risk of hemorrhage (5 of 20 [25%], or 22 per 100 patient years, vs 0 of 10 [0%], or 0 per 100 patient-years, p < 0.05). Three of the 5 hemorrhagic episodes were mild, and in no case was hemorrhage life-threatening. Patients who did not receive warfarin had a greater risk of thromboembolism (2 of 10 [20%], or 12 per 100 patient-years, vs 0 of 20 [0%], or 0 per 100 patient-years, p < 0.05). Both episodes of thromboembolism were life-threatening and necessitated emergency valve replacement. Although warfarin is associated with greater risk of hemorrhage than is acetylsalicylic acid and dipyridamole, warfarin is better than antiplatelet drugs in thromboembolism prophylaxis and is indicated for anticoagulation therapy in children with mechanical cardiac prostheses.