Identification and Basic Management of Bleeding Disorders in Adults

Rebecca Kruse-Jarres, MD; Tammuella C. Singleton, MD; Cindy A. Leissinger, MD

Disclosures

J Am Board Fam Med. 2014;27(4):549-564. 

In This Article

Therapeutic Strategies in Patients With Bleeding Disorders

Preventive Care and Measures

Some basic guidelines apply for all patients with bleeding disorders in the primary care setting. In general, any medication that may impair hemostatic function, such as aspirin and NSAIDs, should be avoided, particularly during bleeding episodes. Proper preventive care, including screening for common age-related comorbidities and associated risk factors, is important in this population. Certain conditions may be particularly problematic in patients with bleeding disorders; for example, untreated severe hypertension may lead to intracranial bleeding.[61] Invasive preventive or screening procedures should not necessarily be deferred because of the risk for bleeding. Routine dental care may be especially important in patients with bleeding disorders to avoid the need for more extensive dental procedures down the line.[62,63] Invasive screening procedures such as colonoscopy may be performed with minimal bleeding risk.[64] Consultation with a hematologist should be considered before such invasive procedures to determine whether systemic hemostatic coverage is indicated and, if so, what this coverage should consist of. Hemostatic therapy often is not needed for minimally invasive procedures, particularly if no tissue incision or excision is required.[64] Meticulous surgical technique and topical measures such as suturing and use of fibrin glue, oxidized cellulose (eg, Surgicel [Ethicon, LLC, San Lorenzo, Puerto Rico]), or topical antifibrinolytics (eg, tranexamic acid) may be sufficient to maintain hemostasis or at least minimize the use of systemic hemostatic treatments in some dental procedures.[65–67] Such topical measures may also be used for bleeding from wounds, in addition to closing (when appropriate), applying pressure to, or packing the wound. Packing can also be used to control epistaxis.[68] With diligent attention to local hemostasis, systemic treatments can often be avoided in cases of minor bleeding.

Hemostatic Therapies. Consultation with a hematologist is strongly recommended before initiating systemic therapies to discuss treatment options and to ensure that samples for all indicated laboratory studies are collected before any blood products are administered, since this may affect the reliability of any results. Transfusion of the missing or defective hemostatic component may not be indicated or effective in all cases. For example, transfusion of platelets may be ineffective in ITP and, in the absence of life-threatening hemorrhage, is contraindicated in microangiopathic conditions such as TTP and in heparin-induced thrombocytopenia, given the risk for exacerbating these conditions and fueling thrombosis.[45,69,70] Similarly, in the setting of liver disease, infusion of large volumes of FFP to treat presumptive coagulopathy may exacerbate bleeding that is a result of elevated venous pressure (eg, variceal bleeding) by further increasing this pressure.[71] In addition, factor replacement may be ineffective in factor deficiencies because of an acquired inhibitor (antibody against the clotting factor concentrate). Other specialized treatments or interventions may be indicated or advised for immediate management of specific bleeding disorders (eg, plasma exchange for TTP or immunomodulatory therapies for immune-mediated thrombocytopenia).

Platelet Transfusion. Indications for platelet transfusion in patients with thrombocytopenia vary based on the underlying mechanism of thrombocytopenia.[41,69,70] Thrombocytopenia as a result of reduced production is an indication for platelet transfusion, and the thresholds for transfusion vary based on the indication ( Table 4 ). There are no such thresholds for platelet transfusion in patients with immune-mediated thrombocytopenia or platelet function defects.[69] Platelet transfusion should only be undertaken in patients with autoimmune thrombocytopenia in instances of serious or life-threatening bleeding (eg, gastrointestinal or intracranial hemorrhage).[69,70] Large amounts of platelets may be required to boost the platelet count in the setting of autoimmune thrombocytopenia, given the shortened survival of the transfused platelets; concomitant administration of immune-modulating therapies such as steroids or intravenous immunoglobulin may attenuate this process, resulting in a more rapid increase in platelet count.[70] Patients with inherited and acquired platelet function abnormalities rarely require platelet transfusion. Alternative measures are proposed as first-line therapies in patients with platelet function defects who are actively bleeding or who require surgery ( Table 4 ), except in cases of severe inherited disorders such as Glanzmann thrombasthenia or Bernard-Soulier syndrome.[68] Human leukocyte antigen–matched platelets may be used in patients requiring multiple transfusions, given the possibility for alloimmunization. If human leukocyte antigen–matched platelets are not available, leukocyte-depleted concentrates may be used.

Coagulation Factor Replacement. For known or suspected coagulation factor deficiencies, factor replacement may be used to treat active bleeding or for hemostatic coverage before surgery. The indications for and necessity of factor replacement vary based on the specific bleeding disorder, the patient's bleeding tendency, the severity of bleeding, and, in the case of invasive procedures, the anticipated risk for bleeding. Because coagulation studies do not necessarily predict surgical bleeding risk in patients without an apparent bleeding disorder, the prophylactic use of factor replacement sources such as FFP simply to correct coagulation study abnormalities before surgery is inappropriate.[26] In fact, prophylactic transfusion of FFP has not been shown to correct coagulation study abnormalities or reduce bleeding risk.[26]

Several options exist for replacing coagulation factors when indicated for treatment or prevention of bleeding[72–75] ( Table 5 ). Given their wide availability, FFP and cryoprecipitate are mainstays of coagulation factor replacement worldwide. FFP is obtained from whole blood or by apheresis and contains all clotting factors.[69] Cryoprecipitate is derived from thawing a single donor unit of FFP at 4°C and is rich in FVIII, VWF, FXIII, and fibrinogen.[72] FFP and cryoprecipitate are primarily indicated for replacement of multiple deficient clotting factors (eg, in DIC) and should be used only to replace single clotting factors when no specific concentrate is available.[69,72] Large volumes of FFP are required to sufficiently boost a single coagulation factor, putting some patients at risk for fluid overload. In addition, despite substantial improvements in donor and plasma screening, transmission of blood-borne pathogens continues to be a theoretical concern with FFP and cryoprecipitate because these products are not subjected to a specific viral inactivation process.[73] Therefore, virally inactivated FFP should be considered when available.[73] For single-factor deficiencies, specific plasma-derived or recombinant factor concentrates are the treatment of choice, when available ( Table 5 ). There are currently no single-factor concentrates for FII, FV, or FX. Prothrombin complex concentrates (PCCs), which are highly purified concentrates of specific coagulation factors (FII, factor IX, and FX ± FVII) obtained from pooled normal plasma, should be used in lieu of FFP for deficiencies of FII or FX, when available, given that PCCs are virally inactivated and contain known amounts of each factor.[74,75] Absent any other source, FFP is the only option for FV replacement; platelet transfusions may be considered as an additional source of FV in cases in which severe bleeding cannot be controlled with FFP alone.[76]

In cases of low factor levels due to an acquired inhibitor, factor replacement may be ineffective, except when the inhibitor titer (autoantibody burden) is very low. Low-titer inhibitors can sometimes be overcome by large amounts of factor. High-titer inhibitors, however, cannot be overcome with large doses of the decreased clotting factor; therefore, so-called bypassing agents are generally recommended for active bleeding (for which they are considered first-line therapy) and for hemostatic coverage during invasive procedures. An activated PCC product and a product containing recombinant activated FVII are the only 2 bypassing agents available. Although neither agent is as effective as replacing the missing factor (when factor replacement is an option), both have been shown to be helpful in achieving hemostasis in patients with coagulation factor inhibitors.[77]

Nontransfusional Hemostatic Therapies. Nontransfusional therapies such as antifibrinolytics (ε-aminocaproic acid or tranexamic acid),[1,25,56,66–68,73,78–86] desmopressin,[21,22,25,35,36,68,77,80,87–91] and vitamin K[92–94] may be used for the treatment or prevention of bleeding in patients with bleeding disorders ( Table 6 ) and occasionally as sole hemostatic agents for the treatment of mild mucosal bleeding or for hemostatic coverage during minor (eg, dental) procedures, thus sparing the patient exposure to transfusional therapies. Nontransfusional therapies can also be used as an adjunct to transfusional therapies in cases of more severe bleeding or for hemostatic coverage during major surgery.

Menorrhagia in women with bleeding disorders often is successfully managed with antifibrinolytics and hormone therapy,[85] including combination or progestin-only contraceptives for maintenance therapy and conjugated estrogens for acute menorrhagia.[25] Transfusional therapies may be used in refractory cases.[25] Invasive options for controlling menorrhagia include the levonorgestrel-releasing intrauterine system, endometrial balloon tamponade, dilatation and curettage, and non-fertility-sparing procedures such as endometrial ablation, uterine artery embolization, and hysterectomy.[25,91]

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