FIVHeMA: Intraventricular fibrinolysis versus external ventricular drainage alone in aneurysmal subarachnoid hemorrhage: A randomized controlled trial

Introduction

Aneurysmal subarachnoid hemorrhage (SAH) is a devastating form of stroke, which often causes acute hydrocephalus requiring the insertion of an external ventricular drain (EVD). A major complication of aneurysmal SAH is delayed cerebral ischemia (DCI). As DCI is linked to the presence of blood within the subarachnoid space, it has been hypothesized that removing this blood may decrease the risk of DCI. This could be achieved by injecting a fibrinolytic agent through the EVD, a strategy called intraventricular fibrinolysis (IVF). Here, we propose to conduct a phase III trial to directly evaluate the impact of IVF after aneurysmal SAH.

Neuropsychological assessments in patients with aneurysmal subarachnoid hemorrhage, perimesencephalic SAH, and incidental aneurysms

Subarachnoid hemorrhage (SAH) is known to be associated with long-term cognitive deficits. Neurosurgical manipulation on the brain itself has been reported to have influence on neuropsychological sequelae. The following is a comparative study on perimesencephalic and aneurysmal subarachnoid hemorrhage patients as well as elective aneurysm patients that was carried out to determine the isolated and combined impact of surgical manipulation and hemorrhage, respectively, on long-term neuropsychological outcome. Inclusion criteria were good neurological recovery at discharge (modified Rankin Scale 0 or 1) without focal neurological deficit. Standardized psychological testing covered attention, memory, executive functions, and mood. Thirteen aneurysmal SAH patients, 15 patients undergoing elective clipping, and 14 patients with perimesencephalic SAH were analyzed. Standardized neuropsychological testing and social/professional history questionnaires were performed 2 years (mean) after discharge. Memory impairment and slower cognitive processing were found in the aneurysmal and perimesencephalic SAH groups, while elective aneurysm patients showed signs of impaired attention. However, compared with norm data for age-matched healthy controls, all groups showed no significant test results. In contrast, signs of clinical depression were seen in 9/42 patients, 45 % of all patients complained of stress disorders and 55 % of patients were unable to work in their previous professions. Nearly normal neuropsychological test results on long-term follow-up in SAH patients were unexpected. However, a 50 % rate of unemployment accompanied with stress disorders and depression manifests insufficient social and workplace reintegration. Therefore, even more specific rehabilitation programs are required following inpatient treatment to attain full recovery.     

Does nimodipine influence sex difference in outcome after aneurysmal subarachnoid haemorrhage?

Summary Before nimodipine was introduced as a standard treatment in patients with aneurysmal subarachnoid haemorrhage (SAH) females had a significantly poorer outcome which might be due to a higher frequency of delayed cerebral ischaemia (DCI). We evaluated the overall outcome with regard to gender in 188 consecutive patients with a verified ruptured intracranial aneurysm treated with nimodipine. The only significant differences concerning prognostic factors between the sexes were a higher frequency of SAH at the primary CT in females (p<0.05) and a higher frequency of middle cerebral artery aneurysms in females (p<0.01). These factors affect the outcome in females unfavourably. However, contrary to previous studies, we found no difference in overall outcome after three months between the sexes in this clinical material. Our observation can be explained by a positive effect of nimodipine on DCI.     

Präoperative Blutungsanamnese

Unexpected bleeding in the perioperative period is largely caused by impaired inherited or drug-induced primary haemostasis. Standard tests for plasma coagulation are predominantly employed to gauge the risk of bleeding. In accordance with several reports the subcommittee for perioperative coagulation (AGPG) of the Austrian Society of Anaesthesia, Resuscitation and Intensive Care (OGARI) recommends the use of a standardised questionnaire to detect an increased risk of bleeding. Accordingly, healthy patients of the American Society of Anesthesiologists (ASA) grades I and II without any suspicion of impaired haemostasis who are scheduled for procedures without expected transfusion requirements, need no standard tests for coagulation. In all other patients (including patients taking medication affecting coagulation, or patients who are unable to provide adequate information) platelet count, platelet function, aPTT, PT, and fibrinogen levels should be assessed.     

Reduced platelet function in subarachnoid hemorrhage

The hypothesis that abnormalities of platelet function may relate to the occurrence or recurrence of subarachnoid hemorrhage (SAH) has been examined. Seventy patients with SAH and 65 control individuals were studied. The adenosine diphosphate (ADP) threshold for secondary platelet aggregation was significantly higher in the SAH group than in the controls. In tests using 4.0 micrograms/ml ADP, the percent platelet aggregation (at 2 minutes) and the maximum rate of platelet aggregation (over 20 seconds) were significantly lower in the SAH patients. There was no difference in total platelet count between the two groups. Platelet adhesiveness was lower in the SAH patients when compared to controls. Circulating microaggregates did not differ between the two groups. The results indicate that reduced platelet function does relate to SAH and may either contribute to aneurysmal rupture in cases of SAH or be a consequence of it.     

Effects of nonsteroidal anti-inflammatory drugs on hemostasis in patients with aneurysmal subarachnoid hemorrhage.

Platelet function is impaired by nonsteroidal anti-inflammatory drugs (NSAIDs) with prominent anti-inflammatory properties. Their safety in patients undergoing intracranial surgery is under debate. Patients with aneurysmal subarachnoid hemorrhage (SAH) were randomized to receive either ketoprofen, 100 mg, three times a day (ketoprofen group, n = 9) or a weak NSAID, acetaminophen, 1 g, three times a day (acetaminophen group, n = 9) starting immediately after the diagnosis of aneurysmal SAH. Treatment was continued for 3 days postoperatively. Test blood samples were taken before treatment and surgery as well as on the first, third, and fifth postoperative mornings. Maximal platelet aggregation induced by 6 microM of adenosine diphosphate decreased after administration of ketoprofen. Aggregation was lower (P < .05) in the ketoprofen group than in the acetaminophen group just before surgery and on the third postoperative day. In contrast, maximal platelet aggregation increased in the acetaminophen group on the third postoperative day as compared with the pretreatment platelet aggregation results (P < .05). One patient in the ketoprofen group developed a postoperative intracranial hematoma. Coagulation (prothrombin time [PT], activated partial thromboplastin time [APPT], fibrinogen concentration, and antithrombin III [AT III]) was comparable between the two groups. Ketoprofen but not acetaminophen impaired platelet function in patients with SAH. If ketoprofen is used before surgery on cerebral artery aneurysms, it may pose an additional risk factor for hemorrhage.     

Association between elevated plasma norepinephrine levels and cardiac wall motion abnormality in poor-grade subarachnoid hemorrhage patients

Patients with aneurysmal subarachnoid hemorrhage (SAH) are frequently complicated by acute cardiac dysfunctions, including cardiac wall motion abnormality (WMA). Massive release of catecholamine into the systemic circulation after aneurysmal rupture is believed to result in WMA, and poor-grade SAH seems to be the most important risk factor. However, plasma catecholamine levels have rarely been measured in SAH patients with WMA, and previous studies indicated that the elevated levels might not necessarily predict WMA. The objective of this study is (1) to evaluate relationship between WMA and plasma catecholamine levels in poor-grade SAH patients in the acute phase and (2) to clarify clinical characteristics of SAH patients with WMA. Among 142 poor-grade (World Federation of Neurosurgical Societies grades IV and V) SAH patients, 48 underwent both transthoracic ultrasound and measurement of plasma catecholamine levels within 24 h of SAH onset. They were divided into WMA+ (n?=?23) and WMA? (n?=?25) groups, and intergroup comparison was made on demographics, plasma catecholamine levels, and outcomes. Plasma norepinephrine levels were significantly higher in WMA+ group than in WMA? group (2,098.4?±?1,773.4 vs. 962.9?±?838.9 pg/mL, p?=?0.02), and the former showed significantly worse outcomes 90 days after admission. There were no intergroup differences in the plasma levels of epinephrine. Plasma norepinephrine levels were inversely correlated with left ventricular ejection fraction. Multivariate logistic regression analysis revealed that increased plasma norepinephrine levels were predictive of WMA, although age, female sex, and grade V SAH were not. This retrospective study highlights the role of norepinephrine in pathogenesis of SAH-induced WMA.     

Preclinical and clinical role of interleukin-6 in the development of delayed cerebral vasospasm and neuronal cell death after subarachnoid hemorrhage: towards a potential target therapy?

Delayed cerebral vasospasm (DCVS), early brain injury (EBI), and delayed cerebral ischemia (DCI) are devastating complications after aneurysmal subarachnoid hemorrhage (SAH). Interleukin (IL)-6 seems to be an important interleukin in the inflammatory response after SAH, and many studies describe a strong correlation between IL-6 and worse outcome. The aim of this study was to systematically review preclinical and clinical studies that evaluated systemic and cerebral IL-6 levels after SAH and their relation to DCVS, neuronal cell death, and DCI. We conducted two systematic literature searches using PubMed to identify preclinical and clinical studies evaluating the role of IL-6 after SAH. Suitable articles were selected based on predefined eligibility criteria following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 61 and 30 preclinical and clinical articles, respectively, were included in the systematic reviews. Of the preclinical studies in which IL-6 was measured in cerebrospinal fluid (CSF), parenchyma, and systemically, 100%, 94.4%, and 81.3%, respectively, showed increased expression of IL-6 after SAH. Preclinical results were mirrored by clinical findings in which elevated levels of IL-6 in CSF and plasma were found after SAH, correlating with DCVS, DCI, and worse outcome. Only two preclinical studies analyzed the direct inhibition of IL-6, which resulted in reduced DCVS and neuronal cell death. IL-6 is a marker of intracranial inflammation and plays a role in the pathophysiology of DCVS and DCI after SAH in preclinical animal models and clinical studies. Its inhibition might have therapeutic potential to improve the outcome of SAH patients.

     

The value of perfusion computed tomography in predicting clinically relevant vasospasm in patients with aneurysmal subarachnoid hemorrhage

Delayed cerebral ischemia remains a severe potential complication of aneurysmal subarachnoid hemorrhage (SAH) possibly leading to death and disability. We evaluated a semiquantitative and visual analysis of perfusion computed tomography (PCT) as a predictor of clinically relevant vasospasm (CRV) in patients with aneurysmal SAH. Thirty-eight patients with aneurysmal SAH were analyzed yielding 145 PCT scans. PCT, clinical examination, and transcranial Doppler ultrasound (TCD) were performed on days 3, 7, 10, and 14 after hemorrhage. Cerebral blood flow, cerebral blood volume, and time to peak (TTP) were analyzed semiquantitatively using six regions of interest, and visually for signs of cerebral hypoperfusion. CRV was defined as secondary cerebral infarction (CI) seen on cranial computed tomography scans and/or delayed neurological deterioration (DND). CI occurred in 13 (34.2 %) and DND in 11 patients (28.9 %). With TCD as pretest, TTP had a sensitivity of 90 % and a specificity of 72 % (cutoff value, 0.963) as predictor for CI. TTP’s sensitivity as predictor for DND was 90 % with a specificity of 61.1 % (cutoff value, 0.983). Visual analysis of TTP showed a negative predictive value of 100 % with a positive predictive value of 52 %. TTP is a sensitive and specific perfusion parameter in predicting CI in patients with SAH. Its use in the clinical setting may optimize the early treatment of patients at risk for vasospasm before the onset of clinical deterioration, especially when applying TCD as pretest. Further investigation in a larger patient population is required.     

Preoperative factors associated with red blood cell transfusion in hip fracture patients

Introduction

Red blood cell (RBC) transfusion is a frequently used treatment in patients admitted with a fractured hip, but the use remains an area of much debate. The aim of this study was to determine preoperative factors associated with the risk of receiving a red blood cell transfusion in hip fracture patients.

Method

The study included 986 consecutive hip fracture patients (aged 60 years or above). The patients were identified from a database of all hip fracture patients admitted to Bispebjerg University Hospital. Data for the database are collected via chart review and data extraction from the hospitals laboratory system, public registries and from the Capital Region Blood Bank Database.

Results

Overall transfusion rate was 58.7 %. The univariate analyses showed that transfusion rate was higher among women (p = 0.004), older patients (p < 0.0001), patients with high ASA scores (p < 0.0001), patients with more severe fractures (p < 0.0001), patients with lower admission haemoglobin levels (p < 0.0001), patients not admitted from own home (p = 0.02) and patients taking aspirin (p = 0.007) or other platelet inhibitors (p = 0.01) on admission. In the multivariate analysis, increasing age, ASA ≥3, being admitted from own home, extracapsular fractures, decreasing admission haemoglobin and use of platelet inhibitors were all significantly associated with the risk of receiving a RBC transfusion.

Conclusion

Several readily available preoperative factors in the form of age, residence, ASA, admission haemoglobin, medication and type of fracture were independently associated with the likelihood of receiving a red blood cell transfusion in patients admitted with a fractured hip.     

Hypomagnesemia after aneurysmal subarachnoid hemorrhage

OBJECTIVE: Hypomagnesemia frequently occurs in hospitalized patients, and it is associated with poor outcome. We assessed the frequency and time distribution of hypomagnesemia after aneurysmal subarachnoid hemorrhage (SAH) and its relationship to the severity of SAH, delayed cerebral ischemia (DCI), and outcome after 3 months. METHODS: Serum magnesium was measured in 107 consecutive patients admitted within 48 hours after SAH. Hypomagnesemia (serum magnesium <0.70 mmol/L) at admission was related to clinical and initial computed tomographic characteristics by means of the Mann-Whitney U test. Hypomagnesemia at admission and during the DCI onset period (Days 2-12) was related to the occurrence of DCI and hypomagnesemia at admission, and hypomagnesemia that occurred any time during the first 3 weeks after SAH was related to outcome. RESULTS: Hypomagnesemia at admission was found in 41 patients (38%) and was associated with more cisternal (P = 0.006) and ventricular (P = 0.005) blood, a longer duration of unconsciousness (P = 0.007), and a worse World Federation of Neurosurgical Societies scale score at admission (P = 0.001). The crude hazard ratio for DCI with hypomagnesemia at admission was 2.4 (95% confidence interval, 1.0-5.6), and after multivariate adjustment it was 1.9 (95% confidence interval, 0.7-4.7). The hazard ratio of hypomagnesemia from Days 2 to 12 for patients with DCI was 3.2 (range, 1.1-8.9) after multivariate adjustment. The crude odds ratio for poor outcome (Glasgow Outcome Scale score, 1-3) with hypomagnesemia at admission was 2.5 (range, 1.1-5.5). Hypomagnesemia at admission did not contribute to the prediction of outcome in the multivariate model. CONCLUSION: Hypomagnesemia is frequently present after SAH and is associated with severity of SAH. Hypomagnesemia occurring between Days 2 and 12 after SAH predicts DCI.     

A randomized controlled study assessing outcome,cognition, autonomy and quality of life in over 70-year-old patients after aneurysmal subarachnoid hemorrhage

Background

Current aging of the population with good physiological status and the increasing incidence of subarachnoid hemorrhage (SAH) in elderly patients has enhanced the benefit of treatment in terms of independence and long-term quality of life (QoL).

Hypotension in anaesthetized patients during aneurysm clipping: not as bad as expected?

Background: Patients with aneurysmal subarachnoid haemorrhage (SAH) often have disturbed autoregulation of cerebral blood flow. A reduction in systemic blood pressure during surgery may therefore lead to delayed cerebral ischaemia (DCI). To assess the incidence and severity of intra-operative hypotension, we performed a retrospective cohort study in 164 patients with recent SAH and surgical clipping of the aneurysm.
Methods: Intra-operative hypotension was defined in three levels of severity, as a decrease in mean arterial pressure (ΔMAP) of more than 30%, 40% or 50% compared with the pre-operative pressure. For each patient the total amount of time with intra-operative hypotension was retrieved. Logistic regression analysis was performed to study the relation between intra-operative hypotension and the occurrence of DCI and poor outcome.
Results: A period with ΔMAP>30% occurred in 128 patients (78%) with a median duration of this period of 105 min (25–75‰ 50–171 min). ΔMAP>40% occurred in 88 patients (54%) and ΔMAP>50% occurred in 22 patients (13%). In univariate analysis, ΔMAP>50% was associated with poor outcome. After adjusting for age and World Federation of Neurological Surgeons grade, the association with poor outcome was no longer statistically significant [odds ratio (OR) 1.018; 95% CI 0.996–1.041].
Conclusion: Hypotension during surgical clipping of intracranial aneurysms occurred frequently. In our study population of patients mostly in good clinical condition, hypotension was not confirmed as an independent risk factor for DCI or poor outcome. Anaesthesia may have had a cerebral protective effect.     

Platelet function following administration of a novel formulation of intravenous diclofenac sodium versus active comparators: a randomized, single dose, crossover study in healthy male volunteers

Study ObjectiveTo assess platelet function and safety following single-dose administration of a novel formulation of intravenous (IV) diclofenac sodium (Dyloject) 37.5 mg versus oral diclofenac 50 mg, IV ketorolac 30 mg, and oral acetylsalicylic acid (ASA) 325 mg.DesignOpen-label, randomized, single-dose, 4-treatment crossover study.SettingClinical research unit.Patients30 healthy, ASA physical status I adult men.InterventionsSubjects were randomized to one of 6 treatment sequences that included 4 single-dose treatments. Study drug administration occurred on Days 1, 3, 5, and 7.MeasurementsPlatelet count, closure time as measured by platelet function analyzer (PFA-100), prothrombin time (PT), activated partial thromboplastin time (aPTT), and plasma concentrations of the study drugs were obtained over 24 hours after each treatment. The primary endpoint was the area under the curve for PFA collagen-epinephrine (CEPI) closure time difference from 0-6 hours post-drug administration (AUC_0-6h). Secondary endpoints included the maximum change from baseline in PFA CEPI closure time.Main ResultsAUC_0-6h (mean ± SD) for CEPI closure time difference was significantly smaller after IV diclofenac 37.5 mg (249 ± 216 sec.hrs) than after ketorolac [and ASA (950 ± 287 sec.hrs and 834 ± 237 sec.hrs, respectively); P ≤ 0.0001 for both] but not after the oral diclofenac control (286 ± 265 sec.hrs; P = 0.40). Similarly, the maximum change from baseline in PFA CEPI closure time was lower after IV diclofenac than after ketorolac or ASA across all time intervals examined. There were no significant changes in PT or aPTT at any time point with any treatment. There was a low frequency of adverse events.ConclusionsAcetylsalicylic acid and ketorolac both substantially disrupted platelet function in contrast to IV diclofenac 37.5 mg or oral diclofenac 50 mg control. Diclofenac, with its balanced COX-1 and COX-2 inhibitory profile, may pose less risk of postoperative bleeding than nonsteroidal antiinflammatory drugs (NSAIDs) such as ketorolac and ASA, which predominantly inhibit COX-1.     

Effect of allopurinol on cardiovascular incidence among hypertensive nephropathy patients: the Gonryo study

Background

The present study aimed to clarify the beneficial effect of allopurinol on cardiovascular morbidity and mortality in a cohort of hypertensive nephropathy patients with impaired kidney function.

Methods

One hundred and seventy-eight patients diagnosed with hypertensive nephropathy and presenting with impaired kidney function (estimated glomerular filtration rate <45 mL/min/1.73 m²) were recruited from nephrology clinics. Oral allopurinol was prescribed in 67 of these patients. The effects of allopurinol use on the development of cardiovascular disease (i.e. ischemic heart disease, congestive heart failure, and stroke) and all-cause death was analyzed using the Cox proportional hazard model.

Results

During the follow-up of 18.4 months (mean), 28 primary events occurred. Basal use of allopurinol was a significant beneficial factor (hazard ratio = 0.342, p = 0.0434, standard error = 0.53058) after adjusting for confounding factors.

Conclusion

The use of allopurinol in hypertensive subjects with impaired kidney function appears to be beneficial in preventing cardiovascular morbidity and all-cause mortality, indicating that this xanthine oxidase inhibitor protects the vascular system, at least in this specific group.     

Delayed cerebral ischaemia after subarachnoid haemorrhage: looking beyond vasospasm

Despite improvements in the clinical management of aneurysmal subarachnoid haemorrhage over the last decade, delayed cerebral ischaemia (DCI) remains the single most important cause of morbidity and mortality in those patients who survive the initial bleed. The pathological mechanisms underlying DCI are still unclear and the calcium channel blocker nimodipine remains the only therapeutic intervention proven to improve functional outcomes after SAH. The recent failure of the drug clazosentan to improve functional outcomes despite reducing vasoconstriction has moved the focus of research into DCI away from cerebral artery constriction towards a more multifactorial aetiology. Novel pathological mechanisms have been suggested, including damage to cerebral tissue in the first 72 h after aneurysm rupture ('early brain injury'), cortical spreading depression, and microthrombosis. A greater understanding of the significance of these pathophysiological mechanisms and potential genetic risk factors is required, if new approaches to the prophylaxis, diagnosis, and treatment of DCI are to be developed. Furthermore, objective and reliable biomarkers are needed for the diagnosis of DCI in poor grade SAH patients requiring sedation and to assess the efficacy of new therapeutic interventions. The purpose of this article is to appraise these recent advances in research into DCI, relate them to current clinical practice, and suggest potential novel avenues for future research.     

Subarachnoid hemorrhage and intracerebral hematoma caused by aneurysms of the anterior circulation: influence of hematoma localization on outcome

Additional space-occupying intracerebral hematoma (ICH) in patients suffering from subarachnoid hemorrhage (SAH) is a known predictor for poor outcome. Emergent clot evacuation might be mandatory. However, data concerning the influence of ICH location on outcome is scarce. Therefore, we analyzed the influence of ICH location on clinical course and outcome in patients with SAH and additional ICH. One hundred seventy-four patients were treated with aneurysmal SAH and additional ICH between September 1999 and May 2012. Information including patient characteristics, treatment, and radiological findings were prospectively entered into a database. Patients were stratified according to ICH location and neurological outcome. Neurological outcome was assessed according to modified Rankin Scale (mRS). ICH location was temporal (58.6 %), frontal (28.7 %), and perisylvian ICH (12.6 %); 63.8 % presented in poor admission status and favorable outcome was achieved in 35.6 %. In the multivariate analysis, favorable outcome was associated with young age, ICH <50 ml, and good admission status. The location of ICH was not associated with outcome. The current data confirms that a significant number of patients with ICH after aneurysm rupture achieve favorable outcome. Prognostic factor for favorable outcome are “age,” “size of the hematoma,” and “admission status.” The location of the ICH seems not to be associated with outcome.     

Thirty-day mortality following total knee arthroplasty over 7 years at a tertiary referral centre of orthopaedic excellence

Total Knee Arthroplasty (TKA) is one of the most successful orthopaedic procedures. Around 100,000 TKAs are performed yearly in the United Kingdom. The aim of this study was to report the mortality rate within 30 days after a TKA in an Orthopaedic Centre of Excellence. We reviewed prospectively collected data of 7067 TKAs performed between April 2009–November 2016. All mortalities within 30 days of a TKA were recorded. Data such as age, sex, ASA, comorbidities and cause of death was recorded. There were 14 (0.198%) deaths within 30 days of TKA. There were eight male patients and six female patients who died. No statistical difference was demonstrated between gender. (p = 0.37). The mean age was 77.9 years (66–94 years). Means days to death from post-op were 9.6 days (2–30 days). One patient was ASA 1, six patients were ASA 2, six patients were ASA 3 and one patient did not have an ASA recorded. There was no statistical difference between the difference ASA groups. (p = 0.27). Cause of death documented was as follow: acute left ventricular failure-3; myocardial infarction-2; pneumonia-2; pulmonary oedema-1; gastrointestinal bleed-1 and multiorgan failure-1. Four patients did not have their cause of death recorded. The 30-day mortality rate after TKA in our institute is low and is comparable to other institutes. This emphasizes that primary TKA is a safe procedure. The predominant cause of perioperative mortality is cardiopulmonary disease.     

Therapieoptionen der perioperativ erworbenen Thrombozytopathie

Increased intra-operative and postoperative blood loss might be caused by acquired platelet function disorders. In particular because conventional coagulation analyses and platelet count fail to detect impaired platelet function, implementation of bedside-tests for platelet function in the peri-operative period is desirable according to the results of retrospective studies. Following adequate adjustment of basic conditions of haemostasis (e.g. temperature, pH, Ca²⁺-concentration, haematocrit) a pharmacological approach with desmopressin (1-desamino-8-d-arginine vasopressin; DDAVP) or tranexamic acid potentially represents a low cost alternative to platelet transfusions with minor side effects.     

Comparison of haemostatic activity in haemodialysis and peritoneal dialysis patients with a novel technique, haemostatometry.

Bleeding due to impaired primary haemostasis is common in uraemia. However, thrombo-embolic episodes are also a clinical problem in dialysis patients. Platelet reactivity to shear stress (haemostasis, H1 and H2), exposure to collagen fibre (thrombus growth) and coagulation of flowing blood (clotting time, CT1 and CT2) were measured in non-anticoagulated blood samples taken immediately before and 18-24 h after haemodialysis (n = 26) and from patients maintained on continuous ambulatory peritoneal dialysis (CAPD, n = 30). H1 (p < 0.001), H2 (p < 0.01), percent thrombus growth rate (p < 0.03), CT1 (p < 0.01 and CT2 (p < 0.05) were restored towards normal after haemodialysis. Results obtained in the CAPD patients demonstrated that the mean values for formation of the haemostatic plug lay between the pre- and posthaemodialysis values; however, CT1 (p < 0.01) and CT2 (p < 0.05) were prolonged in CAPD compared with values after haemodialysis. These data, which indicate platelet function from non-anticoagulated blood and coagulation under flow conditions, (1) confirm that there is impaired haemostasis in uraemia; (2) demonstrate an improvement in haemostasis after haemodialysis; (3) show that peritoneal dialysis results in a haemostatic profile which falls between the pre- and posthaemodialysis pattern, and (4) show that neither dialysis modality returns haemostasis to normal.