Easy bruisability.

Abstract: Physicians often see patients who complain of "easy bruising." The skill of the clinician is to identify those patients likely to have a potentially serious underlying disorder from those who do not. A detailed history often provides sufficient information. A comprehensive physical examination and possibly some baseline laboratory studies can add more data. These tools should permit the clinician to decide if the patient is either basically normal, may have simple contributing factors that lead to bruising, or is at significant risk of bleeding due to the presence of an underlying disorder. In certain circumstances, the situation will prompt the referral to a hematologist or other specialist (gastroenterologist, nephrologist, rheumatologist, endocrinologist, etc.).

Key Words: bruising, easy, bleeding, hemostasis, review, bruisability

The Complaint: "I Bruise Easily"

It is common for physicians to be faced with patients complaining of easy bruisability. Even if bruising is only reported as an incidental finding on the intake questionnaire, it will prompt a more detailed review of the bleeding and coagulation history. The majority of bruises occur as a result of inadvertent or accidental trauma. However, easy bruising can be the hallmark of a hemostatic defect or a systemic illness. For the purposes of this review, patient assessment will not focus on the acutely ill with life-threatening bleeding, but rather on those patients that are seen in the office setting with bruising.

Hemostasis: "Back To Basics"

To assess abnormal bruising, one must first understand the process of normal hemostasis. A bruise is simply the extravasation of blood beneath the surface of the skin that results in discoloration. The skin and subcutaneous tissues are normally natural buffers against external trauma to the blood vessel. Damage that causes bleeding may occur from trauma external to the vessel, internal to the vessel, or of the vessel itself.

Regardless of the cause of the insult, hemostasis begins with local vasoconstriction. The collagen underlying traumatized vascular endothelial cells is exposed to circulating platelets and coagulation factors. Platelets become activated and, with the assistance of von Willebrand factor (vWF) that connects platelet surface glycoproteins to the disrupted endothelial surface, an initial platelet plug is formed. Temporary hemostasis is achieved, but it is only temporary and usually inadequate, in part because of rheologic factors that tend to disturb the platelet plug. Coagulation factors become activated by way of both the intrinsic and extrinsic pathways. Activation of the coagulation cascade will provide a more efficient fibrin plug that effectively traps platelets and permits more permanent hemostasis.

More commonly, bruises occur as a result of trauma due to forces extrinsic to the vessel. However, a patient may suffer from a secondary condition resulting in the disruption of any one of the following anatomic or physiologic defenses against bleeding:

1. Skin

2. Subcutaneous tissue

3. Blood vessels

4. Numbers of platelets

5. Function of platelets

6. Coagulation proteins

Tables 1 and 2 provide detailed lists of abnormalities that may contribute to bruising or bleeding when coupled with extrinsic or accidental trauma. Table 1 groups the disorders based on anatomic or physiologic disruption. Table 2 groups the disorders based on whether or not the abnormality was inherited or acquired. The color of a bruise ("black and blue") will help date its onset. Within a day or two, subcutaneous bleeding is seen as red-brown. Over the subsequent several days, it changes to green (as hemoglobin is converted to biliverdin) and then yellow (as biliverdin is catabolized to bilirubin).

A "Historical Perspective"

Evaluation of the patient with bruising should not focus on laboratory studies. Rather, the assessment centers on a detailed history coupled with a physical examination (Table 3). These tools will typically provide most of the necessary data to determine whether or not there is a need to obtain screening laboratory studies. If laboratory studies are warranted, hopefully the tests that are ordered will be focused to assist the physician in making the correct referral to a hematologist or other specialist.

The history is concentrated on individual components of hemostasis as well as systemic disorders that may affect each part (Tables 1 and 2). It is important to obtain a detailed past medical history as well as determine what comorbid conditions are currently present. For instance, is there an underlying autoimmune disorder (that can directly affect the blood vessel), renal impairment (that may cause dysfunction of platelets), hepatic disease (that may affect the numbers of platelets, platelet function, quantity of coagulation proteins, or the quality of the skin and connective tissue), or thyroid dysfunction (that affects skin and subcutaneous tissue)? Is there a history of a childhood illness? A patient previously treated for a childhood malignancy with chemotherapy and/or radiation may later develop treatment-related bleeding from a marrow disorder such as myelodysplasia or leukemia.

A past history of bleeding (excessive bleeding from childhood cuts or abrasions, epistaxis, menorrhagia, hematuria, rectal bleeding or severe postpartum bleeding) may permit the dating of the disorder as chronic rather than acute or as a congenital disorder as opposed to an acquired one. Has the patient had any previous dental extractions or surgical procedures that resulted in bleeding? If so, did bleeding occur early or late (which focuses on how the hemostatic system generates a clot and the quality of the clot)?

A complete and detailed review of systems should also be obtained. For instance, if the patient reports an intermittent red rash on the cheeks, particularly with sun exposure or hair loss, consideration of a connective tissue disorder would be appropriate. In addition, recent onset constipation and weight gain may be suggestive of hypothyroidism.

Teasing Out the Trauma

Whether the patient is a child or an elderly individual, the physician must consider nonaccidental trauma. Attention to the "home situation," the location of the bruises and the presence of multiple sites can be helpful in determining if further investigation into the patient's social and familial matters is warranted. With children, be aware of their normal development. From age one to three, children will typically sustain bruises appropriate to learning to walk. These are most commonly located on the anterior tibia and knee followed by the upper legs and forehead. However, an infant that is not yet "cruising" who presents with bruising of the hands, trunk or buttocks should prompt consideration of nonaccidental trauma. (1) Lastly, a child that has bruises in the "typical" distribution but seems to "over bruise" in these areas may have an underlying mild coagulation defect.

At the opposite end of the spectrum, elderly patients are also at high risk for bruising. Elders may bruise because of poor skin and subcutaneous tissue turgor, decreased fatty tissue, ambulatory problems relating to cognitive impairment, neurologic or physical disorders, effects of medications and nutritional factors. Indications that should prompt the clinician to delve into the patient's social situation include a patient that appears to be more withdrawn than usual, a caretaker who appears very concerned about the health of the subject and does not want to leave the patient alone, or recurrent bruising in a pattern that cannot be correlated to daily activities or routine daily care. In conclusion, it is essential to keep in mind that the young and the aged are a population at risk for nonaccidental trauma and this must be considered in the evaluation of bruising.

It's "All in the Family"

Be sure to take a detailed family history that is focused on bleeding. Are there any known bleeding problems in the family? A not so obvious "tendency" toward bleeding among family members should also be noted. Oftentimes, a patient will note that "my whole family bruises easily," but denies any personal history of surgical bleeding, excessive bleeding with trauma or a known coagulopathy. A history of female family members with menorrhagia or members of both sexes with bleeding may indicate a nonsex-linked disease such as von Willebrand disease or factor XI deficiency. Bleeding among males and with skipped generations suggests sex-linked disorders such as Factor VIII deficiency (hemophilia A) and factor IX (hemophilia B). These disorders do not occur in females, except for consanguinity and rare acquired antibody disorders. A history of consanguinity may also signal a look for coagulation factor deficiencies that are normally rare, such as autosomal recessively inherited (factor V, factor X and factor XIII) deficiencies. (2) A family member with a history of Ehlers-Danlos is an important clue that skin and subcutaneous disease may be present. Patients who have had a grandparent that "bled to death after an appendectomy" or had a lifelong history of prolonged bleeding from minor cuts would require further evaluation by a hematologist and should not be considered simply an "easy bruiser."

The "Pill Box"

A detailed medication history is most important (Table 4). There are many common medications that predispose patients to bleeding and bruising (aspirin, NSAIDs, steroids, anticoagulants, etc.), but many other medications have the potential to interfere with the coagulation system. The effects of aspirin on platelet function may last for as long as two weeks after discontinuation. Attention should be paid to patients with vascular and heart disease because many of them consider their medications as common cardiac treatment (aspirin, warfarin or enoxaparin) and fail to report them in a drug history. Note the addition of any other antiplatelet function agents (clopidogrel) or NSAIDs (ibuprofen, celecoxib) for other medical conditions. Inhaled, topical and oral steroids can cause alterations in the skin and subcutaneous tissue that result in vascular fragility. (3) SSRIs (paroxetine, sertraline) have been associated with bruising and bleeding due to modulation of the serotonin receptors on platelets. (4,5) Some medications, including anticonvulsants can lead to pancytopenia or isolated thrombocytopenia because of bone marrow aplasia or megaloblastic changes. Antibiotics, particularly with long-term use, can lead to bacterial overgrowth, malabsorption and diarrhea that may result in vitamin K deficiency. Be sure to inquire about the use of over-the-counter medications. Patients may not consider BC Powder or Goody's (aspirin-containing products) that they take a few times a week for headaches or joint aches as medicines. Sometimes a patient is embarrassed about their use of someone else's medication (eg, taking someone else's quinine for leg cramps that may cause thrombocytopenic bleeding). Vitamins and herbal supplements are not regulated by the FDA and can contain ingredients that are known to have a propensity to affect the coagulation system. Finally, herbal preparations may interact with prescribed medications.

Food and Nutrition 

Your approach to this subject depends on the patient sitting before you. If it is a toddler that seems to bruise more than usual even before he or she is just learning to walk, one may wonder if he or she is a "picky" eater. Children who only eat a limited diet (such as macaroni and cheese, chicken fingers and candy) can develop nutritional deficiencies, (6) thereby leading to a coagulopathy, vascular fragility and/or bruising. If the patient is a thin teenage girl, she may be avoiding certain food groups (such as meat or fat) because of an eating disorder that would predispose her to bruising or bleeding. Middle-aged persons may also cut out specific nutrients or food groups; fad diets such as Atkins have gained popularity over the last few years and more people are eliminating fruits and vegetables and adding meats and cheeses to their diets, again leading to nutritional deficiencies over an extended period of time. An elderly person living alone or in a nursing home can develop nutritional problems as well due to poorly fitting or absent dentures, lack of access to certain foods or simply a decreased appetite. Lastly, consider the oral habits that may contribute to bleeding. Is the patient a heavy drinker, smoker or illicit drug user? Does the patient's occupation expose him/her to oral or inhaled toxins?

An Eye for the "Not So" Obvious

The physical examination focuses on important findings and subtleties. The patient's general appearance may provide clues: physiologic age, wasting, jaundice, emotionally wrought, fatigued, pale, etc. Are there signs of systemic diseases (ie, rheumatoid arthritis, leukemia, liver disease, neurologic disorders, etc.)? Is there bleeding at unusual sites such as the oropharynx (often times a finding only with severe thrombocytopenia)? Examination of the skin will allow assessment of the pattern of bruising. Does it occur in dependent areas (thrombocytopenia or stasis factors), only on the arms or legs (trauma or changes in the skin and subcutaneous tissue), or around the eyes (connective tissue disorder)? Aside from bruising, does the skin turgor appear normal? Is the skin thinning and dry (aging, thyroid disease, inherited disorders)? Are the hair and nails brittle (nutritional factors, aging and thyroid diseases)? Are there joint abnormalities suggestive of an underlying rheumatologic disorder? Is there evidence of delayed healing (steroids, thyroid disease, aging) with multiple scars and/or unresolved wounds (Factor XIII deficiency)? Is lymphadenopathy present to suggest a viral illness, or connective tissue disease of a lymphoid malignancy? Is there a heart murmur with resulting petechiae (thrombocytopenia or septicemia)? Is there hepatosplenomegaly to suggest still more possibilities of systemic disease? Are there stigmata of chronic liver disease such as ascites, caput medusa or spider telangiectasias? Specific findings on physical examination, coupled with history, may direct the clinician to order specific laboratory studies that will be outlined below.

Putting It All Together

Thus far, the detailed history and physical examination of patients with "easy bruising" may have permitted the clinician to sort the patient into one of three categories:

1. A healthy individual who may have vascular fragility or trauma but no indication of an underlying bleeding disorder.

2. Someone with one or more factors that likely contribute to slight dysfunction of hemostasis but without evidence of an underlying bleeding disorder.

3. A person with telltale signs or symptoms of a bleeding disorder who may require further evaluation.

Appropriate laboratory studies would include a complete blood count and a peripheral blood smear. Particular attention needs to be directed to the platelet count and hemoglobin, checking the microscopic description for platelet or red blood cell abnormalities, and reviewing the white blood cell count and differential. The PT and aPTT are commonly ordered in this setting but have limited utility. Prolongation of one of the values may be the result of lab error, medication interaction or, less frequently, the presence of a coagulation disorder. In some instances however, the PT and aPTT may be normal despite the presence of an underlying coagulopathy, such as in von Willebrand disease. Therefore, if the clinician has a high index of suspicion that there is an underlying mild bleeding disorder present, then a normal PT and aPTT should not preclude further investigation. (7,8)

In the past, the determination of bleeding times, performed by "template," had been used as a measure of platelet function. These tests are of marginal value and are being replaced. The Platelet Function Analyzer PFA-100 (Dade Behring Inc., Deerfield, IL, USA) test is being used as a more modern method to evaluate platelet function and coagulation factor responsiveness. (9) Although not yet widely commercially available, this type of test will likely have more utility in the future.

Additional testing of the renal, hepatic or endocrine systems can be ordered if there is sufficient evidence to indicate a possible underlying problem. Tests to evaluate the immune system such as electrophoresis or antibody testing can be done, if warranted, but would likely be done in conjunction with a referral to a specialist. Of course, abnormal blood counts, coagulation defects, lymphadenopathy or hepatosplenomegaly would warrant a referral to a hematologist.

References

1. Sugar NF, Taylor JA, Feldman KW. Bruises in infants and toddlers: those who don't cruise, rarely bruise. Arch Pediatr Adolesc Med 1999;153:399-403.

2. Liesner RI, Hann I, Khair K. Non-accidental injury and the haematologist: the causes and investigation of easy bruising. Blood Coagul Fibrinolysis 2004; Vol 15(Suppl 1):S41-S48.

3. Lipworth BJ. Systemic adverse effects of inhaled corticosteroid therapy: a systematic review and meta-analysis. Arch Intern Med 1999;159:941-955.

4. Lake MB, Birmaher B, Wassick S, et al. Bleeding and selective serotonin reuptake inhibitors in childhood and adolescence. J Child Adolesc Psychopharmacol 2000;10:35-38.

5. Pai VB, Kelly MW. Bruising associated with the use of fluoxetine. Ann Pharmacother 1996;30:786-788.

6. Tamura Y, Welch DC, Zic JA, et al. Scurvy presenting as painful gait with bruising in a young boy. Arch Pediatr Adolesc Med 2000;154:732-735.

7. Sham RL, Francis CW. Evaluation of mild bleeding disorders and easy bruising. Blood Rev 1994;8:98-104.

8. George JN, Shattil SJ. The clinical importance of acquired abnormalities of platelet function. N Engl J Med 1991;324:27-39.

9. Kundu SK, Heilmann EJ, Sio R, et al. Description of an in vitro platelet function analyzer: PFA-100. Semin Thromb Hemost 1995;21 (Suppl 2):106-112.

Maria J. Valente, MD, and Neil Abramson, MD

From the Division of Hematology/Oncology, Mayo Clinic, and the Division of Education and Research, Baptist Cancer Institute, Jacksonville, FL.

Reprint requests to Neil Abramson, MD, 1235 San Marco Boulevard, Jacksonville, FL 32207. Email: [e-mail]

Accepted January 13, 2006.

RELATED ARTICLE: Key Points

* Understanding the factors involved in the process of hemostasis (skin, subcutaneous tissue, vascular function, platelet number, platelet function, coagulation proteins) will assist the provider in determining if and where there is a potential problem leading to bruising.

* Emphasis is placed on being aware of the possibility that a patient of any age may be involved in an abusive situation leading to their bruises.

* A complete medical, surgical, family, social and medication history is essential in evaluating a patient with bruising.

* A complete physical examination with direction focused on their distribution and severity will help direct the evaluation.

* Directed laboratory testing can be obtained, but in general, these are helpful if a hemostatic problem and/or an underlying systemic problem is suspected.

Table 1. Disorders associated with bruising

Skin
  Aging
  Steroids
  Ehlers-Danlos syndrome
Subcutaneous tissue
  Aging
  Wasting
  Corticosteroids--exogenous and Cushing disease
  Pseudoxanthoma elasticum
  Ehlers-Danlos syndrome
Vascular
  Connective tissue disease
  Marfan syndrome
  Osteogenesis imperfecta
  Hereditary hemorrhagic telangiectasia
  Vasculitis or cryoglobulinemia
  Amyloidosis
  Aging
Platelet deficiency
  Myeloproliferative disorder
  Lymphoid malignancy
  Autoimmune disorders (ITP, connective tissue disease, etc.)
  Drugs (see Table 4)
  Wiskott-Aldrich syndrome, May-Hegglin anomaly
  Systemic illness (liver disease, myeloproliferative disorder,
    infection)
Platelet dysfunction
  Drugs
  Myeloproliferative disorder
  Von Willebrand disease
  Thrombocytopenia Absent Radius (TAR) syndrome
  Bernard-Soulier
  Glanzmann thrombasthenia
  Storage disease
  Renal disease
Coagulation protein disorders
  Hemophilia (factor VIII, IX, XI deficiency)
  Von Willebrand disease
  Dysfibrinogenemia
  Factor XIII
  Plasmin or plasminogen deficiency or inhibitor
  Circulating anticoagulant or inhibitor
  Vitamin K deficiency, warfarin therapy
  Systemic illnesses (liver disease, amyloidosis)

Table 2. Classification of bleeding disorders

Congenital
  Coagulopathy
    Hemophilia (Factor VIII, IX, XI deficiency)
    Von Willebrand disease
    Congenital fibrinogen disorders (ie. inherited dysfibrinogenemia)
    Factor XIII
    Plasmin/plasminogen deficiency or inhibitor
  Platelet abnormalities
    TAR syndrome
    Bernard-Soulier, Glanzmann thrombasthenia
    Storage disease, Wiskott-Aldrich syndrome
    May-Hegglin anomaly
  Vascular/connective tissue
    Ehlers-Danlos, Marfan syndrome
    Osteogenesis imperfecta
    Hereditary hemorrhagic telangiectasia
Acquired
  Coagulopathy
    Circulating anticoagulant/inhibitor of coagulation factor
    Vitamin K deficiency, warfarin therapy
    Liver/renal disease
    Amyloidosis (Factor X deficiency)
    Myeloproliferative disorders
  Platelet abnormalities
    Medication
    Acquired antiplatelet antibody
    Liver/renal disease
    Myeloproliferative disorder
    Severe systemic illness (sepsis, SIRS, viral)
  Vascular
    Vasculitis/cryoglobulinemia
    Amyloidosis
    Senile purpura
    Medication/nutritional
    Trauma
    Factitious

Table 3. Evaluation of the patient with easy bruisability

History
  Past medical history
    Childhood illnesses
    Cardiac requiring anticoagulation therapy
    Renal or hepatic dysfunction
    Connective tissue or rheumatologic disease
    Gastrointestinal or malabsorptive state
    Deep venous thrombosis requiring anticoagulation
  Past surgical history
    All procedures including dental extractions, circumcision and
      childbirth
    Was there a history of excessive bleeding?
  Bleeding history
    Childhood: excessive bleeding from simple scrapes and cuts
    Mucosal bleeding: epistaxis, gingival, or hemorrhoidal
    Gynecologic: menarche, menorrhagia, postpartum
    Major: hemarthrosis, surgical
  Medications
    See Table 4
    Include over-the-counter medications and herbal supplements
  Family history
    Known bleeding disorder in the family (vWD, hemophilia)
    Gender predilection
    History of a nonspecific bleeding tendency
    History of consanguinity
Physical Examination
  Evaluate the skin
    Pallor to suggest anemia
    Check lips and oral mucosa for telangiectasias
    Purpura or petechiae (thrombocytopenia)
    Location, distribution, size, number, age of bruises
    Hyperextensibility or elasticity
  Evaluate for systemic illness
    Stigmata of liver disease
    Lymphadenopathy or hepatosplenomegaly
    Joint abnormalities
Laboratory Tests
  Complete blood count (CBC) with differential
  Peripheral blood smear for platelet abnormalities
  Prothrombin time/activated partial thromboplastin time (PT/aPTT)
  Serum renal and hepatic profiles
  Serum and urine protein electrophoresis (SPEP/UPEP)
    (especially if age > 50 years)

(a) vWD, von Willebrand disease.

Table 4. Medication, foods, herbs, and easy bruising

Class                     Examples

Anticoagulants            Heparin, low-molecular-weight heparins,
                            warfarin, direct thrombin inhibitors
                            (lepirudin, ximelegatran, argatroban), and
                            factor X inhibitors (fondaparinux)
Antiplatelet drugs        Aspirin, ticlopidine, clopidogrel
Nonsteroidal              Ibuprofen, naproxen, diclofenac, ketorolac,
  antiinflammatory drugs    celecoxib, valdecoxib, meloxicam
Corticosteroids           Prednisone, dexamethasone, fluticasone (nasal,
                            inhaled), hydrocortisone (IV, inhaled,
                            topical), triamcinolone (topical)
Antidepressants           Fluoxetine, paroxetine, sertraline
Antibiotics               Penicillins, cephalosporins, quinine, any
                            broad spectrum antibiotic, or long-term use
Antineoplastics           Cisplatin, cyclophosphamide, doxorubicin
Cardiovascular            Quinidine
Food                      Alcohol, fatty acids
Herbs                     Ginger, gingko, vitamin C, vitamin E, chinese
                            black tree, fungus, garlic (8)