thromboplastin and Acidosis

The increasing understanding of trauma-induced coagulopathy has led to an expansion of treatment strategies in the acute management of trauma patients. The aim of this manuscript is to give a summary of current recommendations for the treatment of trauma-induced coagulopathy based on current literature and valid guidelines. Thetrauma-induced coagulopathyis an independentacutemultifactorial diseasewith significantimpact on the mortalityof severelyinjured patients. Largely responsible for the occurrence and severity of trauma-induced coagulopathy seems to be tissue trauma and shock-induced hypoperfusion. Coagulopathy is amplified by accompanying factors such as hypothermia or dilution. Diagnosis and therapy of deranged coagulation should start as soon as possible. Routinely tested coagulation parameters are of limited use to confirm diagnosis. Therapy follows the concept of "damage control resuscitation". Infusion of large volumes should be avoided and a mean arterial pressure of 65mmHg (in consideration of contraindications!) may be aimed.A specific protocol for massive transfusion should be introduced and continued.Acidaemia should be prevented and treated by appropriate shock therapy.Loss of body temperature should be prevented and treated. Hypocalcaemia <0.9 mmol/l should be avoided and may be treated. For actively bleeding patients, packed red blood cells (pRBC) may be given at haemoglobin<10g/dl(0,62mmol/l). If massive transfusion is performed using fresh frozen plasma (FFP), a ratio of FFP to pRBC of 1:2 to 1:1 should be achieved.For treatment of hyperfibrinolysis after severe trauma the use of tranexamic acid should be considered at an early stage. Fibrinogen should be substituted at levels <1,5g/l (4,41μmol/l). Prothrombin complex concentrates may be helpfull for treatment of diffuse bleeding or anticoagulativemedikation. In acute bleeding, platelets may be transfused at a platet count <100000/μl. For diffuse bleeding or thrombocytopathic patients desmopressin might be a therapeutic option.If a factor XIII (FXIII) measurement is not promptly available, a factor XIII blind-dose should be considered in severe ongoing bleeding. The use of recombinant activated coagulation factor VII (rFVIIa) be considered if major bleeding persists despite standard attempts to control bleeding and best practice use of blood components.

Topics: Acidosis; Antifibrinolytic Agents; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Transfusion; Calcium; Evidence-Based Medicine; Hemodilution; Humans; Hypotension, Controlled; Hypothermia, Induced; Inflammation; Platelet Activation; Resuscitation; Thromboplastin; Wounds and Injuries

Recombinant coagulation factor VIIa (FVIIa) is approved for treating hemophiliacs with inhibitors. High-dose FVIIa has also been used off-label to manage hemorrhage in trauma and surgical patients, many of whom also develop hypothermia and acidosis.. We examined the activity of FVIIa on phospholipid vesicles in the presence and absence of tissue factor (TF) and on platelets as a function of temperature and pH.. FVIIa activity on phospholipids and platelets was not reduced at 33 degrees C compared with 37 degrees C. The activity of FVIIa/TF was reduced by 20% at 33 degrees C compared with 37 degrees C. A pH decrease from 7.4 to 7.0 reduced the activity of FVIIa by over 90% and FVIIa/TF by over 60%.. FVIIa should be effective in enhancing hemostasis in hypothermic patients. However, because the activity of FVIIa is so dramatically affected by pH, its efficacy may be reduced in acidotic patients.

Topics: Acidosis; Adult; Blood Platelets; Factor VIIa; Hemostasis; Humans; Hydrogen-Ion Concentration; Hypothermia; Middle Aged; Phospholipids; Temperature; Thromboplastin

Essentials Acidosis, an outcome of traumatic injury, has been linked to impaired procoagulant efficiency. In vitro model systems were used to assess coagulation dynamics at pH 7.4 and 7.0. Clot formation dynamics are slightly enhanced at pH 7.0 in blood ex vivo. Acidosis induced decreases in antithrombin efficacy offset impairments in procoagulant activity.. Background Disruption of hydrogen ion homeostasis is a consequence of traumatic injury often associated with clinical coagulopathy. Mechanisms by which acidification of the blood leads to aberrant coagulation require further elucidation. Objective To examine the effects of acidified conditions on coagulation dynamics using in vitro models of increasing complexity. Methods Coagulation dynamics were assessed at pH 7.4 and 7.0 as follows: (i) tissue factor (TF)-initiated coagulation proteome mixtures (±factor [F]XI, ±fibrinogen/FXIII), with reaction progress monitored as thrombin generation or fibrin formation; (ii) enzyme/inhibitor reactions; and (iii) TF-dependent or independent clot dynamics in contact pathway-inhibited blood via viscoelastometry. Results Rate constants for antithrombin inhibition of FXa and thrombin were reduced by ~ 25-30% at pH 7.0. At pH 7.0 (+FXI), TF-initiated thrombin generation showed a 20% increase in maximum thrombin levels and diminished thrombin clearance rates. Viscoelastic analyses showed a 25% increase in clot time and a 25% reduction in maximum clot firmness (MCF). A similar MCF reduction was observed at pH 7.0 when fibrinogen/FXIII were reacted with thrombin. In contrast, in contact pathway-inhibited blood (n = 6) at pH 7.0, MCF values were elevated 6% (95% confidence interval [CI]: 1%-11%) in TF-initiated blood and 15% (95% CI: 1%- 29%) in the absence of TF. Clot times at pH 7.0 decreased 32% (95% CI: 15%-49%) in TF-initiated blood and 51% (95% CI: 35%-68%) in the absence of TF. Conclusions Despite reported decreased procoagulant catalysis at pH 7.0, clot formation dynamics are slightly enhanced in blood ex vivo and suppression of thrombin generation is not observed. A decrease in antithrombin reactivity is one potential mechanism contributing to these outcomes.

Topics: Acidosis; Antithrombin III; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Elasticity; Fibrin; Fibrinogen; Healthy Volunteers; Humans; Hydrogen-Ion Concentration; Ions; Proteome; Thrombin; Thromboplastin; Time Factors; Viscosity

Topics: Acidosis; Bicarbonates; Clinical Enzyme Tests; Creatine Kinase; Cryosurgery; Humans; Hyperkalemia; Malignant Hyperthermia; Muscle Rigidity; Musculoskeletal Abnormalities; Myoglobin; Procainamide; Succinylcholine; Thromboplastin

Topics: Acidosis; Adrenocorticotropic Hormone; Animals; Antibodies; Anticoagulants; Antigens; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Volume; Colloids; Cortisone; Endotoxins; Female; Fibrinolysis; Fluorescent Antibody Technique; Hemolysis; Humans; Hyperlipidemias; Kidney Cortex Necrosis; Leukocytes; Mononuclear Phagocyte System; Norepinephrine; Peptide Hydrolases; Phagocytosis; Phenoxybenzamine; Pregnancy; Rabbits; Shwartzman Phenomenon; Sympatholytics; Thromboplastin

Topics: Acidosis; Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Blood Flow Velocity; Blood Transfusion; Blood Volume; Capillaries; Fibrinogen; Fibrinolysis; Humans; Prothrombin Time; Shock, Hemorrhagic; Thrombelastography; Thrombocytopenia; Thromboplastin

Topics: Acidosis; Animals; Blood Coagulation; Blood Coagulation Factors; Blood Coagulation Tests; Dogs; Female; Fibrinolysin; Male; Portal Vein; Thromboplastin