Clinical aspects of coagulation and haemorrhage

Haemorrhage affects all patient groups. Coagulopathy (an abnormality of the clotting system) is closely interlinked with haemorrhage and can either place patients at risk of future bleeding or can exacerbate active ongoing bleeding. There are many causes of coagulopathy – both inherited and acquired. During major haemorrhage, the presence of an acquired coagulopathy increases the likelihood of a poor clinical outcome and a patient is more likely to require large transfusion volumes, critical care admission and is three to four times more likely to die. Other forms of coagulopathy, such as drug-induced coagulopathy (anticoagulant/anti-platelet use) or inherited bleeding disorders, both increase the severity of any active bleeding and place patients at higher risk for future bleeding when exposed to a haemostatic challenge, such as surgery. This risk must be recognized and mitigated. This review focuses on the clinical aspects of coagulation and haemorrhage in all these patient groups.     

Major haemorrhage: past,present and future

Major haemorrhage is a leading cause of morbidity and mortality worldwide. Successful treatment requires early recognition, planned responses, readily available resources (such as blood products) and rapid access to surgery or interventional radiology. Major haemorrhage is often accompanied by volume loss, haemodilution, acidaemia, hypothermia and coagulopathy (factor consumption and fibrinolysis). Management of major haemorrhage over the past decade has evolved to now deliver a ‘package’ of haemostatic resuscitation including: surgical or radiological control of bleeding; regular monitoring of haemostasis; advanced critical care support; and avoidance of the lethal triad of hypothermia, acidaemia and coagulopathy. Recent trial data advocate for a more personalised approach depending on the clinical scenario. Fresh frozen plasma should be given as early as possible in major trauma in a 1:1 ratio with red blood cells until the results of coagulation tests are available. Tranexamic acid is a cheap, life-saving drug and is advocated in major trauma, postpartum haemorrhage and surgery, but not in patients with gastrointestinal bleeding. Fibrinogen levels should be maintained > 2 g.l⁻¹ in postpartum haemorrhage and > 1.5 g.l⁻¹ in other haemorrhage. Improving outcomes after major traumatic haemorrhage is now driving research to include extending blood-product resuscitation into prehospital care.     

Fibrinolytic activity after subarachnoid haemorrhage and the effect of tranexamic acid

Summary Seventy-four patients with recent subarachnoid haemorrhage were randomly allocated to placebo or tranexamic acid treatment. Fibrinolytic activity in the blood and cerebrospinal fluid was assessed before treatment, one week later and two weeks later. The natural history of fibrinolysis following subarachnoid haemorrhage was obtained from analysis of the placebo group.Following subarachnoid haemorrhage, fibrin degradation products and plasminogen activity in the cerebrospinal fluid were elevated. Subsequently, fibrin degradation products in the cerebrospinal fluid fell progressively over the following 2 weeks. Changes in cerebrospinal fluid plasminogen activity correlated with those of blood plasminogen activity.Complications such as rebleeding, hydrocephalus or cerebral thrombosis could not be predicted from analysis of fibrinolytic activity. Tranexamic acid treatment resulted in a reduction in cerebrospinal fluid and blood plasminogen activity. The relevance of fibrinolysis in cerebrospinal fluid and blood to the management of subarachnoid haemorrhage is discussed.     

Clinical aspects of coagulation and haemorrhage

Haemostasis is a complex physiological cascade that results in cessation of bleeding following injury. Inherited bleeding diatheses and hypercoagulable diseases remain a source of patient morbidity that should be recognized and managed. Liver disease should be seen as a heterogeneous group of disorders with unpredictable coagulation affects. The CRASH II trial, recent recommendation by the European Medicines Agency for re-licensing of Trasylol (aprotinin) and the increasing use of novel anti-platelet agents reflect the rapidly evolving haemostatic landscape. Empirical strategies for managing coagulopathy of any aetiology look increasingly flawed as the technology required to tailor therapy to individual situations is now widely available at the point of care.     

Subarachnoid haemorrhage of unknown origin: Clinical and tomographical aspects

Summary 65 patients with negative but technically satisfactory 4 vessel angiography —all admitted to our Department in the years 1976–1983 — were evaluated in the present study. CT scan was undertaken in all cases (in 47 cases within 4 days of haemorrhage). Arterial hypertension was present on admission in 9% of cases. The period of follow-up ranged from 4 to 11 years, with a mean of 5,3 years.The study group was compared to a control group, comprising 760 patients with subarachnoid haemorrhage from ruptured aneurysms, admitted during the same period. Clinical grade on admission (Hunt's classification) was better in patients belonging to the study group. The amount of cisternal deposition on CT scan was less significant than in patients with ruptured aneurysms, and the deposition was often atypical (circumpeduncular, ambiental, and/or tentorial). Clinical deterioration associated with vasospasm was observed in 5% of patients in this study and in 27% of patients in the control group. In patients with a consistent or thick cisternal layer (CT scan at risk) the incidence of clinical vasospasm was 21%, against 47% in controls. One or more rebleedings occurred in 12% of patients in the study group, against 25% of patients in the control group. A significant ventricular dilatation was observed in 15% of patients in the first group (requiring a shunt in 8%), against 25% of patients in the second group (requiring a shunt in 11%). Final outcome was favourable in 95% of patients in this study group and in 63% of patients in the control group, with a mortality rate of 5% in the first group and 32% in the second group.     

Upper gastrointestinal haemorrhage

Upper gastrointestinal (UGI) haemorrhage is bleeding from any point of the GI tract proximal to the ligament of Treitz. There are multiple causes and various presentations, some of which can be quite subtle. With dramatic bleeding, aggressive resuscitation is required in the first instance. The gold standard investigation for diagnosis is endoscopy and this in turn can facilitate certain therapeutic interventions. Other forms of management include radiological and surgical interventions.     

Upper gastrointestinal haemorrhage

Upper gastrointestinal (UGI) haemorrhage is bleeding from any point of the GI tract proximal to the ligament of Treitz. There are multiple causes and various presentations, some of which can be quite subtle. With dramatic bleeding, aggressive resuscitation is required in the first instance. The gold standard investigation for diagnosis is endoscopy and this in turn can facilitate certain therapeutic interventions. Other forms of management include radiological and surgical interventions.     

Effect of antifibrinolytic therapy on subarachnoid fibrosis in dogs after experimental subarachnoid haemorrhage

Summary The effect of antifibrinolytic therapy on posthaemorrhagic subarachnoid fibrosis was observed experimentally in dogs with the scanning electron microscope (SEM). The subchronic subjects, given intravenous injections of tranexamic acid (1 mg/day) for 12 days and sacrificed 3 weeks after cisternal blood injection, showed residual clot with thick fibrosis, especially around the haemorrhage. The chronic subjects, to which the same procedure was applied and which were sacrificed three months after cisternal blood injection, showed significant increases in the subarachnoid fibrosis, most remarkably in the parasagittal region.Tranexamic acid is widely used for preventing the recurrence of subarachnoid haemorrhage. However, it was revealed in this study that antifibrinolytic therapy might increase chronic posthaemorrhagic subarachnoid fibrosis, which is considered to be responsible for communicating hydrocephalus by disturbing epicortical CSF flow⁴.     

Platelet count and transfusion requirements during moderate or severe postpartum haemorrhage

Limited data exist on platelet transfusion during postpartum haemorrhage. We retrospectively analysed a consecutive cohort from a single centre of 347 women with moderate or severe postpartum haemorrhage, transfused according to national guidelines. Twelve (3%) women required a platelet transfusion. There were no differences between women who did and did not receive platelets with respect to age, mode of initiation of labour or mode of delivery. Women receiving a platelet transfusion had a lower median (IQR [range]) platelet count at study entry than women who did not receive platelets before haemorrhage (135 (97–175 [26–259])×10⁹.l^?1 vs 224 (186–274 [91–1006])×10⁹.l^?1), respectively), and at diagnosis of postpartum haemorrhage (median 114 (78–153 [58–238])×10⁹.l^?1 vs 193 (155–243 [78–762])×10⁹.l^?1 respectively). Six women were thrombocytopenic pre‐delivery. The cause of haemorrhage that was associated with the highest rate of platelet transfusion was placental abruption, with three of 14 women being transfused. If antenatal thrombocytopenia or consumptive coagulopathy were not present, platelets were only required for haemorrhage > 5000 ml. Early formulaic platelet transfusion would have resulted in many women receiving platelets unnecessarily. Using current guidelines, the need for platelet transfusion is uncommon without antenatal thrombocytopenia, consumptive coagulopathy or haemorrhage > 5000 ml. We found no evidence to support early fixed‐ratio platelet transfusion.     

Viscoelastic haemostatic point-of-care assays in the management of postpartum haemorrhage: a narrative review

Viscoelastic haemostatic assays provide rapid testing at the bed-side that identify all phases of haemostasis, from initial fibrin formation to clot lysis. In obstetric patients, altered haemostasis is common as pregnancy is associated with coagulation changes that may contribute to bleeding events such as postpartum haemorrhage, as well as thrombosis events. In this narrative review, we examine the potential clinical utility of viscoelastic haemostatic assays in postpartum haemorrhage and consider the current recommendations for their use in obstetric patients. We discuss the clinical benefits associated with the use of viscoelastic haemostatic assays due to the provision of (near) real-time readouts with a short turnaround, coupled with the identification of coagulation defects such as hypofibrinogenaemia. The use of viscoelastic haemostatic assay-guided algorithms may be beneficial to diagnose coagulopathy, predict postpartum haemorrhage, reduce transfusion requirements and monitor fibrinolysis in women with obstetric haemorrhage. Further studies are required to assess whether viscoelastic haemostatic assay-guided treatment improves clinical outcomes, and to confirm the utility of prepartum viscoelastic haemostatic assay measurements for identifying patients at risk of postpartum haemorrhage.     

Control of major haemorrhage

Major haemorrhage defined as ‘life-threatening bleeding’ is associated with significant morbidity and mortality. Prompt and expeditious control of haemorrhage is essential to improve patient outcome and this requires a sound understanding of the fundamental principles of haemorrhage control. Knowledge of the mechanism of injury in trauma and a systematic approach to clinical examination and assessment of blood loss are essential to identify the patient with a life-threatening bleed. Permissive hypotension, correction of coagulopathy and avoidance of hypothermia are important during the resuscitation phase. Special investigations for major haemorrhage are reserved for the haemodynamically stable patient. There are some surgical principles which apply to the various scenarios of major haemorrhage and in particular the concept of damage control surgery is relevant here. Endovascular interventions have added a further dimension to our management strategy. This article aims to discuss some of the principles that govern the management of the patient with major haemorrhage.     

Risk Factors for Reaching the Post-Operative Transfusion Trigger in a Community Primary Total Knee Arthroplasty Population

Background

Little data exist to evaluate an individual’s pre-operative risk of blood transfusion following total knee arthroplasty (TKA). Our aim is to identify the risk factors associated with reaching the transfusion trigger of Hb <8 g/dL (TT8) following surgery and how perioperative tranexamic acid (TXA) affects that outcome.

Evaluation of the Efficacy and Safety of Tranexamic Acid for Reducing Blood Loss in Bilateral Total Knee Arthroplasty

Tranexamic acid (TA) has been reported to reduce blood loss after total joint arthroplasty; however, the literature is sparse in evaluating its efficacy in simultaneous bilateral total knee arthroplasty (TKA). In this retrospective study of consecutive patients, TA use in bilateral TKA was associated with a significant reduction in perioperative serum hemoglobin drop, as well as allogeneic blood transfusion needs from 50% to 11% of patients. No autologous blood donation or drains were used. There were no venous thromboembolic events reported. Implementation of a systematic intravenous TA protocol in simultaneous bilateral TKA appears highly effective in reducing transfusion requirements, potentially reducing healthcare resource utilization as well as the morbidity and complications associated with allogeneic blood transfusions.     

Control of haemorrhage and damage control surgery

Major haemorrhage is associated with significant morbidity and mortality. Prompt recognition and resuscitation is key to improving short- and long-term outcomes and survival. Knowledge of mechanism of injury and potential trauma sustained assists identification of life-threatening bleeding. Management of the patient goes beyond the ‘ABCDE’ approach with a series of clinical interventions known as damage control resuscitation addressing complications of major haemorrhage (coagulopathy, hypothermia and acidosis).Investigations are reserved mostly for the haemodynamically stable patient. For unstable patients the operating theatre is the place to achieve haemostasis by endovascular approaches or damage control surgery (DCS). Damage control surgery sacrifices the completeness of the immediate surgical repair and restoration of anatomy in order to adequately address the combined physiological insult of trauma and subsequent surgery. Surgical strategy in a severely traumatised patient should be considered by the multidisciplinary team prior to operating.Regular discussion between the anaesthetist and surgeon allows progress to be reviewed and realistic goals set for initial surgery. Definitive surgery should be delayed until abnormal physiology is corrected.     

Updates in perioperative coagulation: physiology and management of thromboembolism and haemorrhage

Understanding of blood coagulation has evolved significantlyin recent years. Both new coagulation proteins and inhibitorshave been found and new interactions among previously knowncomponents of the coagulation system have been discovered. Thisincreased knowledge has led to the development of various newdiagnostic coagulation tests and promising antithrombotic andhaemostatic drugs. Several such agents are currently being introducedinto clinical medicine for both the treatment or prophylaxisof thromboembolic disease and for the treatment of bleeding.This review aims to elucidate these new concepts and to outlinesome consequences for clinical anaesthesia and perioperativemedicine.     

A pump-prime aprotinin dose in cardiac surgery: Appraisal of its effects on the hemostatic system

To examine pump-prime aprotinin action on coagulation and fibrinolysis in patients undergoing primary coronary revascularization. A prospective randomized study. A university hospital. Forty-three patients were randomly assigned to either group A, 21 patients treated with 2 × 10⁶ kallikrein inhibitor units (KIU) of aprotinin in the cardiopulmonary bypass (CPB) prime, or group B, 22 patients, untreated. Patients, scheduled for elective coronary surgery, were treated with 2 × 10⁶ KIU of aprotinin in the CPB prime. Markers of coagulation and fibrinolysis were evaluated.

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Surgical times, number of reopenings, and allogeneic blood requirements were collected for each patient. Blood samples were obtained before and after surgery for assessing coagulation (prothrombin time [PT], activated partial thromboplastin time [aPTT], ethanol test, factor VII, antithrombin III [AT III], thrombinantithrombin III complex [TAT], fragment 1.2 of prothrombin [F1.2]) and fibrinolysis (fibrin degradation products [FDP], plasmin-antiplasmin complexes [PAP], D-dimers) markers variations. In group A surgical times were faster, there were fewer reopenings (0 v 3), and fewer blood transfusions (1 patient v 4 patients). The two groups did not differ for PT, aPTT, and fibrinogen measurements. Postoperative FDP (measurable in more patients of group B at the end of the operation), PAP, and D-dimers postoperatory levels (less increased in aprotinin group) show the antifibrinolytic properties of the drug. Regarding the coagulation markers, factor VII decreased, whereas TAT and F1.2 increased, all to a lesser extent in the aprotinin group compared with the untreated patients, at the end of operation. Pump-prime aprotinin minimized, even if not completely inhibited, the activation of coagulation and fibrinolysis during CPB, possibly ensuring a less complicated and safer postoperative recovery. It seemed to allow the maintenance of a correct balance of hemostatic systems, avoiding the risk of thrombotic phenomena.     

Control of major haemorrhage and damage control surgery

Major haemorrhage is defined as ‘life-threatening bleeding’. It is associated with significant morbidity and mortality and prompt, expeditious control of haemorrhage is essential to improve patient outcome. Understanding the mechanism of injury in trauma and a systematic approach to clinical examination and assessment of blood loss are essential to identify the patient with a life-threatening bleed. Permissive hypotension, correction of coagulopathy and avoidance of hypothermia are important during the resuscitation phase. Special investigations for major haemorrhage are reserved for the haemodynamically stable patient. There are some generic surgical principles, which apply to all scenarios of major haemorrhage, and endovascular interventions have added a further dimension to this management strategy. Recent advances in survivability following polytrauma are credited to the modern concept of an integrated approach to damage control resuscitation and damage control surgery. This article aims to discuss some of these key principles that govern the management of the patient with major haemorrhage.     

Cost Benefit Analysis of Topical Tranexamic Acid in Primary Total Hip and Knee Arthroplasty

The purpose of this study was to provide a cost–benefit analysis of topical tranexamic acid (TXA) in primary total hip and knee arthroplasty patients. A retrospective cohort of 591 consecutive patients, 311 experimental and 280 control, revealed a transfusion rate reduction from 17.5% to 5.5%, increased postoperative hemoglobin, and decreased delta hemoglobin without an increase in adverse events (all P< 0.001). This led to saving $83.73 per patient based on transfusion costs alone after accounting for the cost of TXA. Hospital disposition to home compared to subacute nursing facility was also significantly increased by 9.3% (P< 0.02). We conclude that topical TXA reduces transfusion rate, increases home disposition, and reduces cost in primary hip and knee arthroplasty.