What are the differences between hemophilia A, B, and C?
Describe the typical presentation history and pathophysiology associated with von Willebrand disease (vWD).
What plasma protein is important in maintaining normal levels of factor VIII?
What is the difference between platelet adhesion, platelet activation, and platelet aggregation at sites of vascular injury?
Describe the physiologic events that occur following endothelial interruption in the blood vessel.
What prevents the extension of a clot beyond the site of injury?
Describe the procoagulant factors involved in the extrinsic, intrinsic, and common coagulation cascade.
Describe the levels of factor VIII necessary for hemostasis.
Describe the various laboratory tests that evaluate the coagulation cascade and the specific components measured by each.
Would there be any differences in preoperative factor replacement therapy between a patient with hemophilia A and hemophilia B? If so, describe the difference.
What steps would you take to normalize this patient’s coagulation status before surgery?
What is meant by 1 unit of factor VIII clotting activity, and how much does 1 unit of factor VIII clotting activity per kilogram of body weight increase factor VIII concentrations?
Would you administer factor VIII using a bolus or infusion technique?
Can a hemophiliac patient fail to mount an appropriate coagulation response following factor VIII infusion?
If a patient with hemophilia does not respond to a bolus injection of factor VIII, can an infusion technique be effective?
How much factor VIII activity is present in fresh frozen plasma (FFP)? What are the risks associated with administration of FFP?
What are the indications for the administration of FFP?
How is cryoprecipitate prepared? What are the components in cryoprecipitate? How much factor VIII activity is present in cryoprecipitate? What are the indications for cryoprecipitate?
Describe the advantages and disadvantages of the products that are available for transfusion of factor VIII activity.
What is the role of desmopressin D-arginine vasopressin (DDAVP) for hemostatic management in this patient?
What is the role of antifibrinolytic therapy in the perioperative period for the patient with hemophilia? What are examples of antifibrinolytics used in treatment of hemophilia?
Is there a role for recombinant activated factor VII (rFVIIa) in the treatment of hemophilia?
What is the mechanism of action and dosing of rFVIIa?
Is it safe to administer an intramuscular injection to this patient before surgery?
Would an axillary block be appropriate for this patient?
If general anesthesia is used as a technique, would it be safe to intubate the patient’s trachea?
Would you use any special precautions for this patient who is positive for HIV?
What special considerations should be taken in choosing anesthetic drugs for this patient?
During an operative procedure, if the surgeon indicates that significant blood loss is occurring, would you transfuse this patient with packed red blood cells (RBCs) or whole blood?
During the transfusion of the first unit of whole blood, the patient’s temperature rose from 36.8°C to 37.9°C (98.24°F to 100.22°F). What immediate steps should be taken by the anesthesiologist at this time?
Does giving blood intraoperatively increase the potential for the development of factor VIII inhibitors?
Can factor VIII be safely administered to patients who have developed circulating inhibitors?
The surgeon has requested the use of a tourniquet to minimize surgical bleeding. What are the physiologic and hemodynamic responses to tourniquet use?
Is it appropriate to suction the endotracheal tube and oropharynx of this patient before extubation?
What special consideration should be given to postoperative pain management for this patient?
What steps should be taken to enhance the coagulation status of this patient in the postoperative period while at home?
Can this patient be treated with factor VIII supplements using home infusion?
spontaneous development of an autoantibody to factor VIII that occurs in 1:1,000,000 individuals). It is an X-linked recessive disorder and therefore occurs predominately in men and on occasion in homozygous women. Approximately 30% of patients have no family history of this disease; presumably, their disease is caused by a new somatic mutation that results in reduced hepatic protein synthesis. The clinical disease severity (i.e., bleeding diathesis) generally directly correlates both with the factor VIII activity level as well as the presence and efficacy of a neutralizing inhibitor. Patients with less than 1% activity generally express a severe form of the disease, which may manifest as spontaneous bleeding into joints, muscles, and vital organs and involve life-threatening bleeding events (e.g., central nervous system [CNS], retroperitoneum). Patients with between 6% and 40% activity generally have mild disease and may go undiagnosed until they face hemostatic stress. A screening test for hemophilia A is the activated partial thromboplastin time (aPTT), which will be prolonged in all patients except those with mild disease depending on the sensitivity of the coagulation methods/reagents used. Measuring factor VIII activity will generally provide a diagnosis, but reproducibly normal levels do not exclude carrier status because factor VIII concentrations may become elevated in times of stress. Genetic testing provides a definitive diagnosis in the setting of an inherited disorder of protein synthesis.
vWD types and subtypes exist (type 1, type 2A, type 2B, type 2N, type 2M, and type 3). Type 1 and type 3 represent quantitative deficiency of normal vWF related to either modest (type 1) or severe (type 3) reductions in vWF levels due to reduced synthesis. Type 2 includes qualitative defects that are subdivided based on the levels and function of HMW forms of vWF and the corresponding mechanistic defects on platelet adhesion, platelet activation/aggregation, or factor VIII binding. Type 1 vWD represents most afflicted patients (e.g., 85%) and is marked by decreased levels of normal vWF. First-line treatment for type 1 disease is with desmopressin (L-deamino-8-D-arginine-vasopressin [DDAVP]). DDAVP has been shown to frequently normalize vWF and factor VIII levels due to release of vWF from the endothelium as well as other hemostatic factors (i.e., tissue plasminogen activator [tPA], prostacyclin, etc.). Type 2A vWD represents 15% to 30% of type 2 patients and is a qualitative defect in platelet-vWF platelet adhesion. Accordingly, vWF protein levels can be normal, but the absence of HMW vWF multimers results in reduced platelet activation, as reflected by reduced ristocetin induced cofactor activity. Type 2B vWD represents that subset of patients with enhanced affinity for platelet GP Ib, related to a structural abnormality in HMW forms of vWF that result in a more pronounced degree of platelet activation leading to spontaneous platelet aggregation and resultant thrombocytopenia. In these patients, thrombocytopenia may be aggravated by administration of desmopressin. Subtype 2B can be assessed by evaluating the exaggerated response to an antibiotic ristocetin, which stimulates the binding of vWF to platelet GP Ib and resultant platelet aggregation. In the absence of HMW forms of vWF, no agglutination will occur with the ristocetin cofactor activity assay. In type 2N, there is a decreased affinity of vWF for factor VIII based on the absence of the factor VIII binding receptors on vWF. These patients are often misdiagnosed as having hemophilia A. In type 2M, there is a decrease in vWF-dependent platelet adhesion due to an abnormality of HMW multimers. Type 3 vWD is inherited in a recessive fashion and represents virtually complete absence of vWF, and many of these patients die in utero on within a few days after birth. DDAVP is not beneficial in type 3 because these patients have no endogenous production of vWF. Type 2B and type 3 are extremely rare. It is important to distinguish the subtypes of vWD because the use of DDAVP in type 2B may cause worsening of the degree of thrombocytopenia. DDAVP does not increase vWF in type 3 because there are no stores of vWF in endothelial cells.
TABLE 31.1 von Willebrand Disease: Diagnosis, Classification, and Response to Desmopressin D-Arginine Vasopressin (DDAVP)
released. The substances inside the alpha and dense granules include factors such as ADP and serotonin, and factor Va, which further promote platelet activation and aggregation. The platelet plug formed in this process provides initial hemostasis. The degree of platelet activation, release, and ultimate aggregation is in large part predicated by the concentration of thrombin (IIa) in the local milieu. The final stage of platelet plug formation is driven by IIa mediated expression of IIb/IIIa receptors that enables fibrinogen (fibrin) and vWF to crosslink platelets (aggregation). Thrombin also converts fibrinogen to fibrin to strengthen the platelet matrix. Finally, activation of factor XIII produces cross-polymerization of the loose fibrin to produce a firm and stable platelet—coagulation factor cross-linked matrix resulting in a clot.
of thrombin (and hence the amplification of coagulation), its failure to take into account the cellular components, which play a vital role in hemostasis, limits their usefulness in a complete understanding of the hemostatic system.
TABLE 31.2 Levels of Factor VIII Necessary for Hemostasis