ࡱ> kmjW Gzbjbj 2vF]$<<<<P<L   &(((4\ h t$cW ""   &<< &H&t << Coagulopathy PRIVATE  October 22, 1997 Steven L. Shafer, M.D.  Preoperative scenarios: 1. Patient is on chronic aspirin therapy: When should the aspirin be stopped? When is a bleeding time indicated? How does aspirin affect the PT, aPTT, ACT? When is regional anesthesia contraindicated? Any difference in the risk of epidural versus single-shot spinal? How much variation exists between hemostatic responses to aspirin therapy? If the patient is on an NSAID other than aspirin, when should it be stopped? What drugs reverse the effects of aspirin? 2. Patient is on heparin for DVT, 6 weeks following a small PE: How risky is it to stop the heparin? When should the heparin be stopped prior to surgery? Is regional anesthesia contraindicated? Would an axillary block be contraindicated? How would assess residual heparin effect in the O.R.? Is safe to reverse heparin with protamine prior to a regional anesthetic? 3. Patient takes warfarin for chronic atrial fibrillation: When should the warfarin be stopped? How does warfarin affect the bleeding time, PT, aPTT, ACT? Should vitamin K be administered? If major surgery (e.g. AAA repair) is planned, should FFP be administered prophylactically? If so, how much? How about the patient taking warfarin for a mechanical aortic valve? 4. Patient has a history of hemophilia: What is the clinical spectrum of this disease? How does factor VIII level relate to clinical disease? What factor VIII levels are necessary for surgery? What contains factor VIII? What does not contain factor VIII? How does hemophilia affect the bleeding time, PT, aPTT, ACT? 5. Patient has a history of Christmas disease: What is the clinical spectrum of this disease? How common is it? What factor IX level is necessary for surgery? What contains factor IX? What else is this used for? How does this disease affect the bleeding time, PT, aPTT, ACT? 6. Patient has a history of Von Willebrand's disease. What is the clinical spectrum of this disease? How common is it? Why is it important to know the subtypes? How does this disease affect the bleeding time, PT, aPTT, ACT? What therapy might be helpful preoperatively? What therapy might be helpful should bleeding develop intraoperatively? What drugs should they avoid? Intraoperative Scenarios: 1. A hypotensive trauma patient is brought in with a blunt injury to the abdomen. The peritoneal tap in the E.R. is positive for blood. Patient is rushed to the O.R., where a ruptured spleen is removed, and the patient is found to also be bleeding from a pelvic fracture. You have administered 10 units of blood, and the blood pressure has stabilized. What is your a priori expectation that this patient now has a coagulation defect? What clinical observations are relevant to the patients coagulation status? What will an ACT tell you? How does the ACT differ from the aPTT? What additional information will you get from a PT, fibrinogen, fibrin splits, clotting time, etc.? 2. The same patient receives another 10 units of blood over 4 hours. The surgeons are having difficulty obtaining hemostasis. What is your a priori expectation that this patient now has a coagulation defect? What blood products are you going to administer? Who is responsible for the decision of what blood products to give? 3. The patient receives another 15 units of blood over the next 4 hours. The field is very wet. Your catheter sites are oozing. You are now administering every coagulation product known to man. What are all of the coagulation products known to man? What benefits do you expect to get from each of them? How likely is it that the factors in each blood product will address the coagulopathy? What interventions, other than blood products, per se, might help resolve the coagulopathy? Data Base: Coagulation Factors: Final Common Pathway: Think of paper money: X -> V -> II -> I Extrinsic Pathway: Factor X is activated (to Xa) by factor VII. Intrinsic Pathway: Factor X is activated by factors XII, XI, IX, and VIII (e.g. everything else) PRIVATE Factor Name Normal Required Half-life Stability (mg%) (mg%) at 4 degrees I fibrinogen 150-350 70 (50%) 4 days stable II prothrombin 70-130 20 (30%) 2-5 days stable III thromboplastin IV calcium V proaccelerin 70-130 5 (10%) 12 hours 7 days VI activated 5 VII proconvertin 70-150 20 (30%) 300 min stable VIII antihemophilic 50-200 30 (60%) 17 hours 7 days IX Christmas 70-130 20 (30%) 40 hours stable X Stuart 70-130 10 (15%) 40 hours stable XI PTA 70-130 20 (30%) 60 hours 7 days XII Hageman 40-150 0 (0%) stable XIII fibrin stabilizing 50-200 1 (2%) 12 days stable seq Text_Box \* Arabic1 Vitamin K dependent factors: II, VII, IX, X (Not to be confused with the cranial nerves that carry parasympathetic fibers: III, VII, IX, X) Platelets: Thrombocytopenia is the most commonly identified coagulation defect. Maintain platelet count above 50K. Transfuse platelets if platelet count is between 50 and 100K and abnormal bleeding is observed It is difficult to decrease the platelet count to less than 50k with a normal bone marrow. Preoperative platelet count correlates with the amount of blood which can be lost prior to developing thrombocytopenia. Platelets will probably be needed after 1.5 blood volumes. If medical bleeding develops, platelets are the first choice in the absence of laboratory identification of the cause of bleeding. 3-6 units of platelets have about 1 unit of plasma, which contains 50% of usual V, VIII and 80% of other factors. Platelets lasts 5-7 days at room temperature. Platelet concentrates contain some RBC's, which is why ABO typing is needed. Platelet factor III, a phospholipid, activates factor X, using IX and VIII. Pre-existing disorders: Idiopathic Thrombocytopenic Purpura Possibly from antiplatlet antibodies Can occur acutely, especially in kids following viral illness Symptoms: Easy bruising Epistaxis Petechiae G.I. Bleeding Laboratory: Platelet count: 5,000 - 20,000 Bleeding time: prolonged PT: normal PTT: normal Clotting time: normal Treatment: Steroids Splenectomy Usually don't require platelets for splenectomy. If you plan to give platelets, wait until the spleen is out before transfusing them. Secondary Thrombocytopenic Purpura Causes include malignancy (bone marrow invasion), sepsis, collagen disorders, allergic reactions, DIC, and poisoning from insecticides and organic dyes. Laboratory: Platelet count: <60,000 Bleeding time: prolonged Assuming normal platelets, below 100K, Bleeding time (min) = 30.5 - Platelet count/3850 Hemophilia Factor VIII deficiency Prevalence: 1/10,000 to 1/25,000 Sex-linked inheritance PRIVATE Factor VIII Level Symptoms <1% Spontaneous bleeding 3-5% Rare spontaneous bleeding 10-15% Probably asymptomatic until surgery or dental procedures seq Text_Box \* Arabic2 Lab: Bleeding time: normal PT: normal PTT: increased Clotting time: increased Therapy By definition, each ml of FFP contains 1 factor VIII activity unit. Each activity unit transfused raises the activity in the blood by roughly 2%/kg of body weight. So, in a 70 kg patient, each ml of FFP (1 factor VIII activity unit) would raise the activity level by 2%/70 kg = .03%. For surgery we want to have 50% factor VIII activity. We can compute the number of mls as 50% divided by 0.03% bump in factor VIII activity per ml, which equals 1750 mls of FFP (about 9 units). Alternatively, we can use a simple formula to reach 50% factory VIII activity levels as follows: PRIVATE Preparation Factor VIII activity Volume Volume required activity units/ml mls per unit units transfused infusate transfused per kg body weight FFP 1 200 .12 Cryoprecipitate 8 13 .24 seq User_Box \* Arabic1 The transfused units/kg can be calculated as follows: FFP: 50% (target) /2% (bump in activity units/kg) x 1 unit transfused/200 activity units ( 0.12 transfused units/kg Cryo: 50%/2% (bump/kg) x 1 unit transfused/13 mls x 1 ml/8 units factor VIII activity ( 0.24 transfused units Thus, to reach 50% activity levels, a 70 kg adult requires 9 units of FFP (volume = 1800 mls, or 17 units of cryoprecipitate (volume = 221 mls). DDAVP raises factor VIII levels by 2-3 times normal, may be all that is necessary in some mild cases. Danazol (an anabolic steroid) also raises factor VIII levels and has been used, in combination with Amicar, in mild hemophiliacs to avoid transfusions prior to surgery. An even easier rule of thumb is that there are about 15 units of FFP in an adult. To get 50% activity requires about 7.5 units of FFP. Recombinant Factor VIII: Recombinant human antihemophilic factor is now commercially available. Evidently (according to the WWW site of Genetics Institute, Inc) recombinant Factor VIII is the largest protein ever produced using genetic engineering technology. Recombinant Factor VIII is very expensive, but the price will likely drop as more pharmaceutical companies introduce recombinant factor VIII into the market place. Presently there are two products, Kogenate and Recombinate. There is probably no reason to use Factor VIII from donors, now that recombinant Factor VIII is available. Christmas Disease Also known as Hemophilia B Factor IX deficiency Clinically indistinguishable from hemophilia Prevalence: 1/10,000 Sex-linked inheritance Lab: Bleeding time: normal PT: normal PTT: increased Clotting time: increased Therapy: Proplex, Konnyne Risk of hepatitis has been greatly reduced over past 10 years through heat sterilization, treatment with detergents, filtering, and treatment with specific antibodies to remove residual viral particles. BeneFIX Recombinant Factor IX Approved April, 1997 See www.genetics.com for details von Willebrand's Disease Clinically: mild form bleeding disorder, associated with nosebleeds, bruising, increased surgical bleeding, and excessive menstruation. Clotting factors are OK but platelet function is not. Three types: Type 1: Low levels of von Willebrands factor, but the protein is normal. Autosomal dominant, clinically mild Type 2: von Willebrands protein is present but structurally altered. Autosomal dominant. 2A: Large multimers are absent from plasma and platelets 2B: Large multimers have INCREASED affinity for the platelet receptor, resulting in rapid clearance from the plasma Pseudo von Willebrands: looks like 2B, but the problem is not with von Willebrands factor, but with the platelet receptor that has INCREASED affinity for the von Willebrands factor. End result is the same: rapid clearance of von Willebrands factor from plasma. Type 3: von Willebrands protein is absent. Autosomal recessive. Types 2 and 3 are most severe. Lab: Bleeding time: prolonged PT: normal PTT: normal Clotting time: normal or prolonged Lab results may be normal and repeated testing required to establish diagnosis. Tests such as the ristocetin cofactor, antibody assay to the von Willebrands factor, ristocetin-induced platelet for aggregation (RIPA), FVIII assay, and bleeding time are used to separate types I, 2, and 3. Treatment: Cryoprecipitate FFP transfusion has a sustained beneficial effect. DDAVP 0.3 to 0.4 mcg/kg normalizes bleeding time for Type 1 and 2A von Willebrands Contraindicated in type 2B and pseudo von Willebrands disease because it will cause platelet aggregation and thrombocytopenia. Amicar and Cyclokapron are useful for 5-7 days after bleeding episodes. Miscellaneous Factor Disorders Factor I deficiency (fibrinogen) sex-linked inheritance PT: increased PTT: increased Factor VII deficiency autosomal recessive Bleeding time: normal PT: prolonged PTT: normal Factor X deficiency (Stuart factor) Bleeding time: increased PT: increased PTT: increased Uremia Causes platelet dysfunction Bleeding time may increase 3 to 4 fold May be reversible with DDAVP or cryoprecipitate. Liver failure In complete failure, patients may require 2 units of FFP every 2 hours to maintain adequate hemostasis. Preoperative Drug Therapy: Warfarin Factor 7 is the first factor depleted, which is why the PT is affected before the aPTT. Warfarin has a half-life of 40 hours. Warfarin-like effect from broad-spectrum antibiotics, probably from interference with bacterial flora. Vitamin K usually corrects a Vitamin K dependent coagulopathy in 6 - 12 hours. If PT is less than twice normal, it may be safer to operate than to risk the thrombosis that the patient has been placed on coumarin to prevent. For emergency surgery, or when vitamin K is contraindicated (e.g. artificial valvular prosthesis), use 2 units of FFP, then check PT. Aspirin Aspirin is in many combination medications, e.g. cold remedies. Patient's may not realize they have been taking aspirin. As high as 50% of patients undergoing unexpected surgery have a history of recent aspirin ingestion. If patient is otherwise normal, aspirin usually prolongs the bleeding time by 1.5 - 2 minutes. If patient has an undiagnosed, otherwise asymptomatic, disorder (e.g. heterozygous von Willebrand disease), a single aspirin can increase the bleeding time to > 30 minutes. Stop aspirin 3-4 days prior to surgery. DDAVP is effective in normalizing the prolonged bleeding time caused by aspirin. If urgent surgery, transfuse platelets at least 90' after the last dose of aspirin to allow it to clear from the circulation. Heparin Binds antithrombin III with thrombin, inactivating thrombin. Blocks activation of factor X, XI, IX. Small doses initially inhibit factor IX, which is why the aPTT is prolonged before the PT is affected. Can cause thrombocytopenia, which is sometimes profound. Regional versus General Anesthesia in the anticoagulated patient: (from Cousins) Epidural: Only 1 case in which an epidural hematoma followed an epidural anesthetic when coagulation status was normal. 100 cases of spontaneous epidural hematomas in anticoagulated patients with no history of instrumentation of the epidural space. Two studies, with 4164 patients receiving heparin during and after (but not before) surgery found no incidence of epidural hematomas (Oberg & Thoren, Acta Physiol Scand 85:164, 1972; Rao & El-Etr, Anesthesiology 55:616, 1981). The catheter was placed the night prior to surgery. Avoid epidurals if platelet count is less than 100,000, or if the bleeding time is greater than 8 minutes. If a patient brought to the O.R. is on heparin, "epidural block is not used in any form." Key is to look for evidence of neurologic sequelae, and than rapidly evaluate it and decompress the spinal cord should sequelae develop. Spinal: Gross abnormality in blood clotting mechanisms is considered to be an absolute contraindication to spinal anesthesia. Minor abnormalities (e.g. mini-dose heparin prior to surgery) is a relative contraindication to spinal anesthesia. Tests of hemostasis: WATCH FIELD FOR BLEEDING! Whole blood clotting time a red top tube in your pocket should clot in less than 15 minutes clot dissolution (especially within 20 minutes) suggests DIC can be done in O.R. PT Monitors extrinsic pathway (factor VII) Used for warfarin monitoring because first factor depleted is factor VII. aPTT Measures intrinsic pathway. Responds to heparin effect first because of heparin's inhibition of factor IX. Usually just called the PTT, but it is actually a different test. PTT is not done routinely any more. Factor XII activation is variable and can skew results dramatically. Includes contribution of platelets (in the form of platelet factor 3) Phospholipid micelles mimic the platelet function in the PTT. "activated" to shorten the time of the test and eliminate the variable activation of factor XII. Citrated plasma is mixed with diatomaceous earth, which converts XII into active XIIa. After mixing everything together (plasma, phospholipid micelles, diatomaceous earth), the clot is timed from the addition of CaCl2 to the formation of clot. ACT (activated clotting time) Measures same pathway (intrinsic) as the aPTT. May be a better measurement of in vivo activity because the whole, uncitrated, blood is used, and the patient's platelets are used are used instead of micelles. Not used outside of the O.R. because the test must be run immediately after drawing the sample. Useful to subsequently observe the clot for lysis. INR: (International Normalized Ratio) Calculated as EMBED Equation. Generally want to have below 1.2 Rapaport Scale: Level 1: Negative history, minor operation. No tests necessary. Level 2: Negative history, major operation. aPTT and platelet count. Level 3: Suspicious history, or operation which requires unusually good hemostatic function (e.g. open prostatectomy, bypass): platelet count, aPTT, PT, Bleeding time. Level 4: Known coagulation defect: specific factor assays. Blood products: Whole blood If less than 5 days old, contains some clotting factors and active platelets Factors V and VIII start to degrade after 24 hours Packed red blood cells Hct: 57-88% (mean: 73%) Stored at 4 degrees centigrade. One third of the amount of fibrinogen in whole blood. Otherwise, contains no significant amounts of clotting factors or platelets. Platelets Stored at room temperature. Platelet levels start to fall after 4 hours of cold storage. Nearly normal factor levels. Indications for platelet transfusion: Platelet count less than 20,000 (except in ITP patients undergoing splenectomy) Platelet count less than 60,000-70,000 in patients scheduled for surgery Patients with a bleeding time greater than 12-15 minutes, regardless of platelet count. Patients whose transfused blood volume exceeds about 1.5 blood volumes. Pump runs greater than 2 hours. Large tissue injuries may cause a functional defect in platelets, independent of dilutional and consumptive thrombocytopenia. Each unit contributes 5000 platelets/ul at 1 hour. Indications per Stanford QA Program: Platelet count less than 20,000/mm3 Platelet count less than 50,000/mm3 with active bleeding Platelet count less than 100,000/mm3, + high risk bleeding (e.g. CNS, eye) Platelet dysfunction (e.g. uremia) and active bleeding or surgery Acute massive bleeding Splenectomy, may give 20 units preoperatively For ECMO or CPB within 24 hours of procedure. Fresh Frozen Plasma Major justification is to give factor VIII. Factor VIII rapidly synthesized in response to injury. Maintain PT between 12 and 15. Consider FFP after 1.5 - 2 blood volumes. Not indicated for: Volume expansion To reconstitute pRBCs. Routine administration of FFP is increasingly controversial. Your body contains about 12 units of FFP. Thus, 12 units of FFP should fully restore normal coagulation. Indications per Stanford QA Program: Congenital coagulation disorders, liver disease, Coumadin overdose DIC, nephrotic syndrome, newborn hemorrhagic diathesis, septic shock, protein losing enteropathy, plasmapheresis, newborn exchange transfusion, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome "Suspected coagulopathy due to deficiency of soluble coagulation factors in a patient who is bleeding where coagulation studies are pending at the time of infusion." During surgery or active bleeding if PT > 18, PTT > 45 "Active bleeding with blood loss > 20%" During CPB or ECMO with TT > 17 "Other indications." Cryoprecipitate Major justification is to give factor VIII. Also useful in von Willebrands Factor VIII: 80 units Fibrinogen: 230 mg Other factors: none is significant quantities. Fibrinogen is stable in banked blood. If fibrinogen is low, it is very unlikely to be from dilutional coagulopathy, since pRBC, FFP, and platelets all contain fibrinogen. Therefore, low fibrinogen is probably from DIC. shelf life: 6 months Usual indication is severe hypofibrinogenemia from DIC Indications per Stanford QA Program: Documented Factor VIII deficiency History of prolonged APTT Von Willebrand's disease Hypofibrinogenemia and active bleeding Active bleeding in a uremic patient During CPB or ECMO with TT > 17, reptilase clotting time > 14 DIC or Septic Shock "Other indications." Recombinant Factor VIII: Kogenate and Recombinate Factor IX Concentrates Contain factor II, VII, IX, X (the vitamin-K dependent factors). May also contain activated factors, and can cause thrombotic complications with intense use. Use only for documented factor IX deficiency, or for bleeding unresponsive to other measures, as infusion itself can lead to DIC! Might be useful as a specific antidote to warfarin, except that the risk of hepatitis approaches 100%, and FFP works well for restoring vitamin-K dependent factors. Trade names: Proplex, Konyne Recently approved recombinant factor IX: BeneFIX Indications per Stanford QA Program: Documented factor II, VII, IX, X deficiency in bleeding or surgical patient Documented high Factor VIII inhibitor in bleeding or surgical patient PT > 1.5 times normal DDAVP (vasopressin) Yes, I know it is not a blood product, but I didn't know where else to put it. Increases factor VIII and von Willebrand's factor by releasing them from endothelial cells. Factor VIII levels may peak 2-3 times higher than baseline. Second dose within 48 hours of first dose will have reduced response because intercellular stores must be replenished. May normalize Taspirin induced coagulopathy. May correct uremic coagulopathy. Reduces postoperative blood loss following cardiac surgery Buy stock today. Fibrinolytics Aprotinin Nonspecific serine protease inhibitor extracted from bovine lung. Discovered in 1930 Contact activation during CPB mediated by kallikrein system activation of intrinsic pathway on contact with pump material causes thrombin formation impairs platelet adhesive function High dose blocks contact activation protects platelet adhesive receptors preserves platelet aggregation in synergy with heparin, prevents thrombin formation Low dose: just blocks fibrinolysis, cheaper drugs may do just as well Raises ACT as an artifact. Maintain ACT >750? Perhaps us a different test of heparin activity. Reserved for complex cases with long anticipated CPB time. At Stanford often used for redo surgery. Synthetic antifibrinolytic amino acids: EpsilonAminocaproic acid (EACA) para aminomethylbenzoic acid (PAMBA) tranexamic acid Useful to treat excessive bleeding following cardiac surgery Only action is antifibrinolysis, no protective effect as found with aprotenin Amicar is often used in routine cardiac surgery to reduce transfusion requirements. Rational Transfusion Therapy: Does it exist? Mathematically, 30% of the original blood elements are still present after 1 blood volume of hemorrhage and replacement. Clinically, the percentage is closer to 40%. "Routine replacement of clotting factors and platelets based on the volume of blood transfused is difficult to justify" - John Collins (Former Chairman, Stanford Department of Surgery), World J. Surg. 11:75-81, 1987 "Clearly red cell transfusions should be freely supplemented with platelet and/or concentrated coagulation components for the correction of underlying hemostatic deficiencies if such are considered contributory to hemorrhage." V. Lovric, Anaesth Intens Care 12:246-251, 1984. "It would be wasteful to administer platelets prophylactically to all patients for a condition that, at most, may affect only one out of 16 (6.25%) of those with massive transfusion, and for a condition that is so readily and effectively treated when it occurs." R. Reed, Ann Surg 203:40-48, 1986 "There appears to be no clear advantage to the prophylactic infusion of platelets in comparable patients ... who receive massive transfusions but do not have medical bleeding." C Harrigan, et al, 98:836-843, 1985 "The mathematics of exchange transfusion would support the contention that specific hematologic derangements attributable to massive transfusion per se should not become critical until a patient has received a transfusion volume of approximately twice his estimated blood volume." T Phillips, J Trauma 27:903-910 "Important principles include ... the administration of platelets to trauma patients ... receiving 12 or more units of rapid transfusion, especially those who have been truly massively transfused with volumes of 20 units or more; and the administration of FFP to those receiving large volumes of factor free fluids." T Phillips, J Trauma 27:903-910 "Where the wound is large .... or where there is head injury, [we recommend] administration of FFP ... on a one-to-one ratio with pRBC to avoid dilutional coagulopathy." J Hewson, et al, Crit Care Med 13:387-391, 1985 "Pending controlled studies in man, the routine use of plasma supplementation in the resuscitation regimen for hemorrhagic shock should be abandoned." D. Martin, et al, Ann Surg 202:505-511, 1985 "Although the concentrations of factor V and particularly factor VIII are reduced in stored whole blood, concentrations in massively transfused patients do not correlate with the number of transfusions and remain sufficiently high to support the coagulation cascade. Concentrations of other soluble coagulation factors are not affected by massive transfusions of stored whole blood." in "Massive Transfusion" (chapter 56), from Hemostasis and Thrombosis, 1987. I was unable to find any studies which justify a cookbook approach to platelet and FFP administration. As the above quotations indicate, there is controversy within the surgical and anesthetic literature regarding routine administration of these products. However, the clinical reality is that, in the massively transfused patient, relevant laboratory data may not be available when the decision is made to treat what appears to be medical bleeding. Rational therapy involves a trade off between an intellectually satisfying approach (administer dangerous drugs only for clear indications) and the time constraints of resuscitating a patient who is bleeding to death. Rational therapy is also an explicit admission that in situations in which there are no useful therapeutic options for the patient, treating ourselves may still be in the patient's best interest. Also, the O.R. is not a rational place to debate transfusion policy with the surgeons. Rough Guidelines: Monitor the surgical field for evidence of medical bleeding If that is observed and is causing you or the surgeons concern, in the absence of other data, administer platelets. After 1 blood volume: Check whole blood clotting time Check ACT Send off PT, aPTT, platelet count, and fibrinogen level. Order platelets After 1.5 blood volumes: Repeat whole blood clotting time, ACT Order FFP Specific situations: Massive transfusion Dilutional thrombocytopenia is the most likely cause of medical bleeding. Rarely, bleeding may be caused by a deficiency in factors V of VIII. Very rarely, bleeding from dilution of other factors. If fibrinogen is low, it is probably because of DIC and not from dilution. Disseminated intravascular coagulation Refractory coagulopathy is common after massive transfusions and probably caused by prolonged hypotension, hypoperfusion, and vascular damage. Fibrinogen is rapidly consumed by thrombin, producing fibrin. Fibrin is rapidly degraded by plasmin, producing fibrin split products. Fibrin split products interfere with clot formation. Diagnosis: Bleeding diathesis platelet count < 80K low fibrinogen elevated fibrin split products Other lab results: TT (thrombin time): increased PT: increased PTT: increased Clot time: greater than 10 minutes, shouldn't subsequently lyse. Marked decrease in factors V, and VIII also. Treatment: Treat the underlying disorder Platelets FFP Cryoprecipitate Concentrated factor I and VIII. Factors most likely depleted. Needed in the highest level for adequate hemostasis. Lost most rapidly from banked whole blood, red cells, and platelets. Vitamin K Nothing may be effective. Amicar is contraindicated. "From 4 to 6 h, by which time ongoing surgical bleeding has usually been brought under control, our data clearly revealed a very close correlation between coagulation and ... antecedent shock" J. Hewson, et al, Crit Care Med 13:387-391, 1985 Hypothermia Inhibits platelet function. Platelet counts decrease. Decreases enzyme activity leading to clot formation. Fibrinolytic activity increases. Acid-base imbalance Enzymes are sensitive to pH. Anybody have any references to specific acid-base effects on hemostasis? I couldn't find any references. Citrate toxicity Calcium is an essential cofactor for coagulation. However, I could find no documentation that the serum calcium ever drops so low as to contribute to a coagulopathy. Any data or references would be appreciated. Autotransfusion No associated coagulopathy from recycled blood as long as it is washed. Extracorporeal circulation: The pump eats platelets. Small amounts of fibrin form in the perfusion circuit despite adequate heparinization. Neutralize heparin with protamine, 1.0 mg for every 100U of heparin. Heparin rebound 2-3 hours after protamine, possible from different rates of elimination of the drugs. Factors V and VIII are depleted during bypass, but usually not enough to require FFP. FFP Contents: Take contents in plasma (table 1) and adjust for 200 cc!  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