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Clinical Evaluation of Bleeding and Bruising in Primary Care DANA NEUTZE, MD, PhD, and JODI ROQUE, MD, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

Bleeding and bruising are common symptoms in the primary care setting. The patient history can help determine whether the bruising or bleeding is abnormal. The International Society on and has devel- oped a bleeding assessment tool that can be used to indicate possible pathology. A family history of bleeding problems may suggest a hereditary defect. Such a history is especially important in children who may not have experienced a major bleeding episode. Medication review can identify pharmacologic causes of the bleeding or bruis- ing. Physical examination findings such as mucocutaneous bleeding suggest that the underlying condition is caused by dysfunction, whereas hemarthroses or are more common in . If the history and physical examination findings suggest a , initial laboratory testing includes a complete count, peripheral blood smear, prothrombin time (PT), and partial thromboplastin time (PTT). A normal PT and PTT indicate a platelet disorder, the most common of which is . A normal PT and prolonged PTT signal a deficit in the intrinsic pathway, and a mixing study should be performed. A challenge is indicated in patients with an abnormal PT and normal PTT. A workup for liver failure is warranted in patients with prolonged PT and PTT. If initial testing does not reveal an etiology in a patient with a high suspicion for a bleeding disorder, the patient should be referred to a hematologist for additional evaluation. (Am Fam Physician. 2016;93(4):279-286. Copyright © 2016 American Academy of Family Physicians.)

CME This clinical content asy bruising and abnormal bleeding Mechanisms of Bleeding and Bruising conforms to AAFP criteria are common symptoms in the pri- Bleeding occurs when there is a disruption for continuing medical education (CME). See mary care setting that may present in walls. In healthy individu- CME Quiz Questions on as excessive bruising when injured, als, if the endothelial defect is not too large, page 264. Eor as epistaxis, menorrhagia, or prolonged exposed subendothelial proteins interact Author disclosure: No rel- bleeding during or dental proce- with coagulation factors and to form evant financial affiliations. dures. It is estimated that 26% to 45% of clots. Petechiae are the result of blood leak- ▲ Patient information: healthy patients have a history of epistaxis, age from a small number of blood vessels. A handout on this topic, easy bruising, or gum bleeding.1 Approxi- Bruising is when a forms under written by the authors of mately 5% to 10% of reproductive-aged the skin as the result of vascular damage. this article, is available women seek treatment for menorrhagia,2 at http://www.aafp.org/ History and Physical Examination afp/2016/0215/p279-s1. and an estimated 29% of these women have html. an underlying bleeding disorder.3,4 Women BLEEDING HISTORY with von Willebrand disease are five times The age and sex of the patient should be con- more likely to have menorrhagia than those sidered when evaluating those with abnor- without the condition.5 Although von Wil- mal bruising and bleeding. Severe inherited lebrand disease affects men and women bleeding disorders often manifest in infancy equally, women are more likely to seek eval- or early childhood. Women are more likely uation because of heavy menses. to report bleeding because of menses and Identification of bleeding and bruising childbirth, even in the absence of a bleed- and appropriate intervention can decrease ing disorder. The patient should be asked to the associated morbidity and mortality. describe the type of bleeding or bruising (i.e., Evaluation of the patient with bleeding and epistaxis, menorrhagia, or hematomas) and bruising requires a detailed personal and the circumstances surrounding the bleeding family history, a thorough review of medi- (e.g., trauma, dental procedures, surgery). cations, physical examination, and labora- The physician should determine whether tory testing. any blood products, medications (e.g., oral

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SORT: KEY RECOMMENDATIONS FOR PRACTICE

Evidence Clinical recommendation rating References

The ISTH-BAT should be used during the initial evaluation of patients with a C 11, 12 suspected bleeding disorder. A peripheral blood smear, , prothrombin time, partial C 18-20 thromboplastin time, and renal and liver function tests should be obtained in patients with an abnormal ISTH-BAT score or in whom a bleeding disorder is suspected. Patients should be referred to a hematologist for further evaluation if suspicion C 15 for a bleeding disorder remains high despite a negative workup.

ISTH-BAT = International Society on Thrombosis and Hemostasis Bleeding Assessment Tool. A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp.org/afpsort.

contraceptives), or other hemostatic treat- validated in prospective studies. Based on ments (e.g., antifibrinolytic inhibitors, des- a study of 1,040 adults and 328 children, mopressin, recombinant products) were the normal ISTH-BAT cutoff is 3 for men, used to treat the bleeding. 5 for women, and 2 for children.13 The tool is Physical abuse should be ruled out, par- administered by a clinician or trained per- ticularly if the bruising has an abnormal sonnel and takes approximately 20 minutes. pattern and there is clinical suspicion. Addi- A modified,self-administered tool may be tional information about nutritional status, available in the near future.14 alcohol use, liver or kidney disease, and The ISTH-BAT was designed primarily recent illnesses or infections can provide for identification of congenital disorders of useful diagnostic clues about the underly- hemostasis. It is less helpful for identifying ing etiology, particularly if the bleeding or inherited platelet function disorders (sen- bruising is new in onset (Table 1).6,7 sitivity = 49%; specificity = 53%; positive likelihood ratio = 1.04).15 Thus, if suspicion BLEEDING ASSESSMENT TOOLS of a bleeding disorder is high, evaluation by Several different bleeding assessment tools a hematologist is warranted. (BATs) have been developed to quantify the patient’s subjective experience of bleeding FAMILY HISTORY and bruising. These tools have sensitivities X-linked recessive hemophilias or von Wil- of 41% to 100% and specificities of 81% to lebrand disease should be considered in 99%, with positive likelihood ratios ranging patients with a family history of bleeding. It from 2 to 71 and negative predictive values is important to ask about several generations greater than 99%.5,8-10 To reduce variability and second-degree relations, such as mater- between tools, the International Society on nal uncles, when hemophilia is suspected in Thrombosis and Hemostasis (ISTH) cre- a male. However, a negative family history ated a standardized tool for use in adults and does not exclude a genetically inherited dis- children,11 which is summarized in Table 2.12 order; up to one-third of patients diagnosed (The full tool is available for free at http://c. with hemophilia have no family history.16 ymcdn.com/sites/www.isth.org/resource/ Similarly, a negative family history does not resmgr/ssc/isth-ssc_bleeding_assessment. preclude someone from having von Wil- pdf.) Although the ISTH-BAT is based on lebrand disease, because incomplete pene- previous validated bleeding tools and ret- trance and variable expression contribute to rospective studies, it has yet to be fully the complexity of inheritance. Obtaining a

280 American Family Physician www.aafp.org/afp Volume 93, Number 4 ◆ February 15, 2016 Bleeding and Bruising Table 1. Clinical Clues for Bleeding or Bruising Disorders

Clinical clues Possible etiology

Acute illness/hospitalization* , neurologic abnormalities (aphasia, hemiplegia, mental status changes, Thrombotic thrombocytopenic (rare) seizures, paresthesia, visual disturbance, renal dysfunction) reaction, infection, malignancy, pancreatitis, Disseminated intravascular coagulation (rare) (preeclampsia, acute postpartum hemorrhage, septic abortion)

Infection Infectious diarrhea in children (Escherichia coli O157:H7), renal dysfunction Hemolytic uremic syndrome Upper respiratory tract infection, arthralgias, gastrointestinal symptoms (typically Henoch-Schönlein purpura in children)

Inherited/autoimmune syndromes Epistaxis, gingival bleeding, and menorrhagia, often with lifelong bleeding but von Willebrand disease negative laboratory test results (prothrombin time, partial thromboplastin time) Hypermobile joints with dislocations, hyperextensibility of skin Ehlers-Danlos syndrome (collagen disorder), other connective tissue disease Joint/soft tissue bleeding in men Hemophilia A (factor VIII) or B (factor IX), other factor deficiency Malar rash, arthralgias, family history of autoimmune disorders Systemic lupus erythematosus Telangiectasias (lips, , nasal cavity, skin, gastrointestinal tract), epistaxis Hereditary hemorrhagic telangiectasia (Osler-Weber- Rendu syndrome) Viral infection; may be asymptomatic or show signs of mucocutaneous bleeding if Idiopathic (immune platelet count is low thrombocytopenic purpura)

Malignancy Lymphadenopathy, renal failure, splenomegaly Hematologic malignancy

Nutrition Alcohol use, ascites, gynecomastia, scleral icterus, spider angioma, splenomegaly Alcoholic Poor nutritional intake (fruits and vegetables) Vitamin C deficiency (scurvy),

Physiologic/external forces Bruising on upper thighs and arms (often in women) Purpura simplex (easy bruising) Report of injury or atypical pattern of bruising inconsistent with history; bruising Physical abuse in children who are not mobile; in the pattern of objects Thin skin with dark ecchymosis, often in older adults (most typically over extensor Senile purpura surfaces of arms)

Pregnancy-related Preeclampsia Hemolysis, elevated liver enzyme levels, low platelet count syndrome

NOTE: Many of the signs and symptoms may overlap between different etiologies. If a specific cause of bleeding is suspected, pursue further directed workup. *—These conditions cause a combination of clotting and bleeding. Information from references 6 and 7. thorough family history is especially impor- patients are taking a drug that can cause tant in children because they may not have bleeding or bruising, the possibility of an challenged their clotting system with sur- underlying bleeding disorder should not be gery or dental procedures. dismissed. Some medications may be clini- cally indicated despite increased bleeding MEDICATION HISTORY and bruising (e.g., [Plavix] after An evaluation of prescription and over- coronary stenting). Physicians must dis- the-counter medications and supplements cuss the risks and benefits of these medica- is important to identify pharmacotherapy- tions with patients. Additional evaluation induced bleeding (Table 3).17 Even when is warranted if a medication is suspected

February 15, 2016 ◆ Volume 93, Number 4 www.aafp.org/afp American Family Physician 281 Bleeding and Bruising Table 2. International Society on Thrombosis and Hemostasis Bleeding Assessment Tool

Score Symptoms (to the time of diagnosis) 0* 1* 2 3 4

Epistaxis None/ More than five per year or lasting Consultation only† Packing, , or Blood transfusion, replacement therapy (use of trivial longer than 10 minutes antifibrinolytic therapy hemostatic blood components and recombinant activated factor VII), or desmopressin therapy

Cutaneous None/ At least five bruises (> 1 cm) in Consultation only† Extensive Spontaneous hematoma requiring blood transfusion symptoms trivial exposed areas

Bleeding from None/ More than five per year or lasting Consultation only† Surgical hemostasis Blood transfusion, replacement therapy, or minor trivial longer than 10 minutes desmopressin therapy

Oral cavity None/ Present Consultation only† Surgical hemostasis or antifibrinolytic Blood transfusion, replacement therapy, or symptoms trivial therapy desmopressin therapy

Gastrointestinal None/ Present (not associated with Consultation only† Surgical hemostasis or antifibrinolytic Blood transfusion, replacement therapy, or bleeding trivial , portal hypertension, therapy desmopressin therapy hemorrhoids, or )

Hematuria None/ Present (macroscopic) Consultation only† Surgical hemostasis or iron therapy Blood transfusion, replacement therapy, or trivial desmopressin therapy

Tooth extraction None/ Reported in 25% or less of all Reported in more than Resuturing or packing Blood transfusion, replacement therapy, or trivial procedures; no intervention‡ 25% of all procedures; desmopressin therapy no intervention‡

Surgery None/ Reported in 25% or less of all Reported in more than Surgical hemostasis or antifibrinolytic Blood transfusion, replacement therapy, or trivial procedures; no intervention‡ 25% of all procedures; therapy desmopressin therapy no intervention‡

Menorrhagia None/ Consultation only,† changing pads Missed work/school Combined antifibrinolytic and hormone Acute menorrhagia requiring hospital admission trivial more frequently than every two more than twice per therapy, or present since menarche and emergency treatment; blood transfusion, hours, clotting and flooding, or year; antifibrinolytic, and longer than 12 months replacement therapy, or desmopressin required; score higher than 100 on pictorial hormone, or iron or dilation and curettage, endometrial ablation, or blood loss assessment chart§ therapy hysterectomy required

Postpartum None/ Consultation only,† oxytocin Iron or antifibrinolytic Blood transfusion, replacement therapy, Any procedure requiring critical care or surgical hemorrhage trivial (Pitocin) use, or lochia lasting therapy desmopressin therapy, or requiring intervention (e.g., hysterectomy, internal iliac longer than six weeks examination under anesthesia and/or artery ligation, uterine artery , uterine the use of uterine balloon/package to brace sutures) tamponade the uterus

Muscle Never Post-trauma, no therapy Spontaneous, no Spontaneous or traumatic, requiring Spontaneous or traumatic, requiring surgical hematomas therapy desmopressin or replacement therapy intervention or blood transfusion

Hemarthrosis Never Post-trauma, no therapy Spontaneous, no Spontaneous or traumatic, requiring Spontaneous or traumatic, requiring surgical therapy desmopressin or replacement therapy intervention or blood transfusion

Central nervous Never — — Subdural, any intervention Intracerebral, any intervention system bleeding

Other bleeding¶ None/ Present Consultation only† Surgical hemostasis, antifibrinolytic Blood transfusion, replacement therapy, or trivial therapy desmopressin therapy

*—The distinction between 0 and 1 is of critical importance; 1 means that the symptom is judged as present in the patient’s history but does not qualify for a score 2 or higher. †—The patient sought medical evaluation and was referred to a subspecialist or offered detailed laboratory investigation. ‡—For example, a score of 1 is assigned for four extractions/ in which only one resulted in bleeding (25%); a score of 2 is assigned for one extraction/surgery resulting in bleeding (100%), for two extractions/surgeries in which only one resulted in bleeding (50%), or for three extractions/ surgeries in which only one resulted in bleeding (33%). §—If already available at the time of collection. ¶—Includes umbilical stump bleeding, , cheek hematoma caused by sucking during breast/bottle feeding, conjunctival hemorrhage, and excessive bleeding after circumcision or venipuncture. When these conditions occur in infants, detailed investigation is required independent from the overall score.

282 American Family Physician www.aafp.org/afp Volume 93, Number 4 ◆ February 15, 2016 Bleeding and Bruising Table 2. International Society on Thrombosis and Hemostasis Bleeding Assessment Tool Table 3. Medications that Cause Bleeding or Bruising

Score Mechanism of action Drugs Symptoms (to the time of diagnosis) 0* 1* 2 3 4 Coagulation (Eliquis),* dabigatran (Pradaxa),* inhibition enoxaparin (Lovenox),* heparin, Epistaxis None/ More than five per year or lasting Consultation only† Packing, cauterization, or Blood transfusion, replacement therapy (use of (Xarelto),* (Coumadin)* trivial longer than 10 minutes antifibrinolytic therapy hemostatic blood components and recombinant Collagen degradation Corticosteroids activated factor VII), or desmopressin therapy Platelet function Aspirin/nonsteroidal anti-inflammatory drugs,* inhibition clopidogrel (Plavix),* fish oil, selective serotonin Cutaneous None/ At least five bruises (> 1 cm) in Consultation only† Extensive Spontaneous hematoma requiring blood transfusion symptoms trivial exposed areas reuptake inhibitors Alcohol, antibiotics (cephalosporins, linezolid [Zyvox], Bleeding from None/ More than five per year or lasting Consultation only† Surgical hemostasis Blood transfusion, replacement therapy, or nitrofurantoin, penicillin, rifampin, sulfonamides, minor wounds trivial longer than 10 minutes desmopressin therapy vancomycin), carbamazepine (Tegretol), quinine, thiazide diuretics, valproic acid (Depakene) Oral cavity None/ Present Consultation only† Surgical hemostasis or antifibrinolytic Blood transfusion, replacement therapy, or symptoms trivial therapy desmopressin therapy *—Most commonly causes bleeding.

Gastrointestinal None/ Present (not associated with Consultation only† Surgical hemostasis or antifibrinolytic Blood transfusion, replacement therapy, or Information from reference 17. bleeding trivial ulcer, portal hypertension, therapy desmopressin therapy hemorrhoids, or angiodysplasia)

Hematuria None/ Present (macroscopic) Consultation only† Surgical hemostasis or iron therapy Blood transfusion, replacement therapy, or as the cause of bleeding and bruising, but trivial desmopressin therapy symptoms persist beyond seven to 10 days despite discontinuation of the medication. Tooth extraction None/ Reported in 25% or less of all Reported in more than Resuturing or packing Blood transfusion, replacement therapy, or trivial procedures; no intervention‡ 25% of all procedures; desmopressin therapy Antiplatelet and anticoagulation agents no intervention‡ most commonly cause bleeding or bruising. Drug-induced thrombocytopenia should be Surgery None/ Reported in 25% or less of all Reported in more than Surgical hemostasis or antifibrinolytic Blood transfusion, replacement therapy, or suspected when the platelet count rebounds trivial procedures; no intervention‡ 25% of all procedures; therapy desmopressin therapy no intervention‡ after discontinuation of the drug in question and decreases with reexposure to the drug.17 Menorrhagia None/ Consultation only,† changing pads Missed work/school Combined antifibrinolytic and hormone Acute menorrhagia requiring hospital admission Although low platelet counts can occur in trivial more frequently than every two more than twice per therapy, or present since menarche and emergency treatment; blood transfusion, hours, clotting and flooding, or year; antifibrinolytic, and longer than 12 months replacement therapy, or desmopressin required; patients with heparin-induced thrombocy- score higher than 100 on pictorial hormone, or iron or dilation and curettage, endometrial ablation, or topenia (an immune-based thrombocytope- blood loss assessment chart§ therapy hysterectomy required nia), the major complication is thrombosis

Postpartum None/ Consultation only,† oxytocin Iron or antifibrinolytic Blood transfusion, replacement therapy, Any procedure requiring critical care or surgical rather than bleeding. hemorrhage trivial (Pitocin) use, or lochia lasting therapy desmopressin therapy, or requiring intervention (e.g., hysterectomy, internal iliac longer than six weeks examination under anesthesia and/or artery ligation, uterine artery embolization, uterine PHYSICAL EXAMINATION the use of uterine balloon/package to brace sutures) A thorough physical examination may yield tamponade the uterus information about the origin of bleeding. Muscle Never Post-trauma, no therapy Spontaneous, no Spontaneous or traumatic, requiring Spontaneous or traumatic, requiring surgical Hemophilia or other congenital bleeding hematomas therapy desmopressin or replacement therapy intervention or blood transfusion disorders should be considered in patients Never Post-trauma, no therapy Spontaneous, no Spontaneous or traumatic, requiring Spontaneous or traumatic, requiring surgical with spontaneous hemarthroses, muscle therapy desmopressin or replacement therapy intervention or blood transfusion hemorrhages, or retroperitoneal bleeding. Mucocutaneous bleeding (e.g., petechiae, Central nervous Never — — Subdural, any intervention Intracerebral, any intervention system bleeding epistaxis, gingival bleeding, gastrointestinal or genitourinary bleeding) suggests a plate- Other bleeding¶ None/ Present Consultation only† Surgical hemostasis, antifibrinolytic Blood transfusion, replacement therapy, or let disorder. Hepatomegaly suggests liver trivial therapy desmopressin therapy failure, whereas splenomegaly may suggest underlying malignancy. Although extremely *—The distinction between 0 and 1 is of critical importance; 1 means that the symptom is judged as present in the patient’s history but does not qualify Adapted with permission from Rodeghiero F, Tosetto A, rare, splenomegaly can be consistent with for a score 2 or higher. Abshire T, et al.; ISTH/SSC joint VWF and Perinatal/Pedi- idiopathic thrombocytopenic purpura. †—The patient sought medical evaluation and was referred to a subspecialist or offered detailed laboratory investigation. atric Hemostasis Subcommittees Working Group. ISTH/ ‡—For example, a score of 1 is assigned for four extractions/surgeries in which only one resulted in bleeding (25%); a score of 2 is assigned for one SSC bleeding assessment tool: a standardized question- extraction/surgery resulting in bleeding (100%), for two extractions/surgeries in which only one resulted in bleeding (50%), or for three extractions/ naire and a proposal for a new bleeding score for inher- Laboratory Evaluation surgeries in which only one resulted in bleeding (33%). ited bleeding disorders. J Thromb Haemost. 2010;​8(9):​ 2063-2065. If the ISTH-BAT score is above the sex- and §—If already available at the time of collection. age-specific cutoff, laboratory evaluation ¶—Includes umbilical stump bleeding, cephalohematoma, cheek hematoma caused by sucking during breast/bottle feeding, conjunctival hemorrhage, and excessive bleeding after circumcision or venipuncture. When these conditions occur in infants, detailed investigation is required independent from should be performed. In a young child who the overall score. has not yet had a challenge to the clotting system, a strong family history would be a

February 15, 2016 ◆ Volume 93, Number 4 www.aafp.org/afp American Family Physician 283 Bleeding and Bruising

reason to perform laboratory testing. Ini- A peripheral smear serves several purposes tial testing with a complete blood count, in a bleeding workup. First, it can confirm peripheral blood smear, prothrombin time whether thrombocytopenia is present because (PT), and partial thromboplastin time (PTT) automatic analyzers can under- or overesti- can indicate possible disorders in plate- mate platelet counts if the platelets are smaller lets or the clotting cascade, thus narrow- or larger than normal.18 Additionally, ethyl- ing the differential diagnosis (Figure 1).18-21 enediaminetetraacetic acid, one of the anti- Renal and liver function testing is also coagulants used in automatic analyzers, can indicated. cause pseudothrombocytopenia secondary

Evaluation of Abnormal Bleeding and Bruising Patient presents with abnormal bleeding or bruising

Rule out trauma or medications as possible cause (Table 3)

Clinical clues to guide workup (Table 1)

Abnormal score on ISTH-BAT (order complete blood count, peripheral blood smear, PT, PTT, renal and liver function tests)

Abnormal Abnormally low Normal PT? platelet platelet count size/shape Yes No Thrombocytopenia If specific Normal PTT? Normal PTT? disorder not evident Yes No Yes No

A PTT mixing study Administer vitamin K Liver function testing Factor VIII (if not already done) von Willebrand factor antigen Consider factor assays von Willebrand factor activity Corrects Does not correct Corrects Does not correct

Liver disease Factor VIII, IX, XI assays Lupus Malnutrition Factor VII assay Disseminated intravascular Factor VIII inhibitor Normal Abnormal coagulation If factor VIII low Factor deficiency

Light transmission von Willebrand aggregometry* disease Go to A

Platelet function disorders

*—This test should be ordered only by a hematologist.

Figure 1. Algorithm for the evaluation of abnormal bleeding and bruising. (ISTH-BAT = International Society on Throm- bosis and Hemostasis bleeding assessment tool; PT = prothrombin time; PTT = partial thromboplastin time.) Information from references 18 through 21.

284 American Family Physician www.aafp.org/afp Volume 93, Number 4 ◆ February 15, 2016 Bleeding and Bruising

to platelet clumping. Finally, observation of factors (VIII, IX, and XI) vs. clotting fac- platelet morphology and characteristics can tor inhibitors, namely factor VIII inhibitor provide important information regarding and lupus anticoagulant. Normal plasma possible hematologic malignancies or hyper- is mixed with the patient’s plasma in a 1:1 proliferation conditions.19 ratio and the PTT is retested. The PTT gen- erally corrects after mixing and stays cor- NORMAL PT/NORMAL PTT rected after incubation if there is a clotting A normal PT and PTT indicate that the clot- deficiency, but will prolong after incubation ting cascade is intact, unless there is a mild if there is a clotting inhibitor. There are no factor deficiency. Therefore, further evalua- standardized methods of interpretation or tion should focus on platelet function activ- cutoff values for these studies; therefore, the ity. Bleeding time is no longer considered sensitivity and specificity can vary between the test of choice because it is labor intensive laboratories.25 It is important to determine and has poor sensitivity and specificity. The which calculations and cutoffs are used by platelet function analyzer (PFA-100), devel- the laboratory when interpreting the results. oped in the 1990s, automates the process of It is important to note that factor VIII determining platelet aggregation by pass- levels can be low in persons with von Wil- ing the patient’s blood through two mem- lebrand disease in the setting of a mildly pro- branes. Although the PFA-100 can detect longed PTT. Thus, it is worth screening for severe forms of von Willebrand disease, the disorder with a mixing study.24 it may miss milder, more common forms of the condition, with a sensitivity of only ABNORMAL PT/NORMAL PTT 61.5% to 71%.20 Additionally, the PFA-100 A prolonged PT in the setting of a normal has variable sensitivity for detecting platelet PTT is uncommon26 and suggests an abnor- function abnormalities (24% to 81%).22,23 mality in the extrinsic pathway. Vitamin K Therefore, it is not recommended by the administration with normalization of the ISTH as a screening tool for von Willebrand PT can rule out a vitamin K deficiency. If the disease or platelet function disorders.21 PT remains prolonged, evaluation of factor Von Willebrand disease, a disorder of VII should be undertaken. platelet aggregation, is the most common cause of inherited . Thus, if ABNORMAL PT/ABNORMAL PTT the PT and PTT are normal, the next step Prolongation of the PT and the PTT suggests is testing for von Willebrand factor antigen, liver failure, disseminated intravascular von Willebrand factor activity (also called coagulation, or defects in the common path- ristocetin cofactor activity), and factor VIII way to the intrinsic and extrinsic pathways. level.21,24 If any of these are abnormal, fur- The appropriate evaluations to discern these ther testing should be performed to deter- causes are liver function tests (if not already mine the type of von Willebrand disease. performed), fibrinogen levels, and testing This can be carried out by a hematologist, factor assays, respectively. if desired. If screening is negative, light transmission aggregometry is the preferred Referral diagnostic test for platelet function disor- The patient should be referred to a hema- ders.21 Because this test is labor and resource tologist if initial laboratory testing is not intensive, it should be ordered only by a definitively diagnostic of a bleeding disor- hematologist.19 der, but a high clinical suspicion remains.15 In addition, a preoperative evaluation that NORMAL PT/ABNORMAL PTT reveals abnormal laboratory findings should A prolonged PTT with a normal PT indicates prompt a delay in surgery until evaluation is an abnormality in the intrinsic pathway. The complete or consultation is obtained. next step is to perform a PTT mixing study The authors thank Anthony Viera, MD, MPH, and George to distinguish abnormalities in the clotting Fedoriw, MD, for their assistance with the manuscript.

February 15, 2016 ◆ Volume 93, Number 4 www.aafp.org/afp American Family Physician 285 Bleeding and Bruising

Data Sources: A PubMed, Cochrane review, and UpTo- 11. Tosetto A, Castaman G, Plug I, Rodeghiero F, Eiken- Date search was completed using the key terms bleeding, boom J. Prospective evaluation of the clinical utility of bruising, coagulopathy, and von Willebrand. The search quantitative bleeding severity assessment in patients included meta-analyses, clinical trials, and reviews. referred for hemostatic evaluation. J Thromb Haemost. Search dates: January and November 2015. 2011;9 ( 6):1143-1148. 12. Rodeghiero F, Tosetto A, Abshire T, et al.; ISTH/SSC joint VWF and Perinatal/Pediatric Hemostasis Subcom- The Authors mittees Working Group. ISTH/SSC bleeding assessment tool: a standardized questionnaire and a proposal for DANA NEUTZE, MD, PhD, is an assistant professor at the a new bleeding score for inherited bleeding disorders. University of North Carolina at Chapel Hill Family Medicine J Thromb Haemost. 2010;8(9):2063-2065. Residency Program. 13. Elbatarny M, Mollah S, Grabell J, et al.; Zimmerman Pro- JODI ROQUE, MD, is an assistant professor at the Uni- gram Investigators. Normal range of bleeding scores for versity of North Carolina at Chapel Hill Family Medicine the ISTH-BAT: adult and pediatric data from the merg- ing project. . 2014;20(6):831-835. Residency Program, and also practices at Piedmont Health Services, Prospect Hill (N.C.) Community Health Center. 14. Deforest M, Grabell J, Albert S, et al. Generation and opti- mization of the self-administered bleeding assessment Address correspondence to Dana Neutze, MD, PhD, Uni- tool and its validation as a screening test for von Wil- versity of North Carolina at Chapel Hill, 590 Manning lebrand disease. Haemophilia. 2015;21(5):e384-e388. Dr., Chapel Hill, NC 27599 (e-mail: dana_neutze@med. 15. Lowe GC, Lordkipanidzé M, Watson SP; UK GAPP study unc.edu). Reprints are not available from the authors. group. 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286 American Family Physician www.aafp.org/afp Volume 93, Number 4 ◆ February 15, 2016