Find information on thousands of medical conditions and prescription drugs.


Cryoglobulinemia is the presence of abnormal proteins in the bloodstream which thicken or gel on exposure to cold.


These proteins may be present in mycoplasma pneumonia, multiple myeloma, certain leukemias, primary macroglobulinemia, and some autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis.

C syndrome
Café au lait spot
Calcinosis cutis
Canavan leukodystrophy
Canga's bead symptom
Canine distemper
Carcinoid syndrome
Carcinoma, squamous cell
Cardiac arrest
Carnitine transporter...
Caroli disease
Carpal tunnel syndrome
Carpenter syndrome
Cartilage-hair hypoplasia
Castleman's disease
Cat-scratch disease
CATCH 22 syndrome
Cayler syndrome
CDG syndrome
CDG syndrome type 1A
Celiac sprue
Cenani Lenz syndactylism
Ceramidase deficiency
Cerebellar ataxia
Cerebellar hypoplasia
Cerebral amyloid angiopathy
Cerebral aneurysm
Cerebral cavernous...
Cerebral gigantism
Cerebral palsy
Cerebral thrombosis
Ceroid lipofuscinois,...
Cervical cancer
Chagas disease
Charcot disease
Charcot-Marie-Tooth disease
CHARGE Association
Chediak-Higashi syndrome
Childhood disintegrative...
Chlamydia trachomatis
Cholesterol pneumonia
Chorea (disease)
Chorea acanthocytosis
Choroid plexus cyst
Christmas disease
Chromosome 15q, partial...
Chromosome 15q, trisomy
Chromosome 22,...
Chronic fatigue immune...
Chronic fatigue syndrome
Chronic granulomatous...
Chronic lymphocytic leukemia
Chronic myelogenous leukemia
Chronic obstructive...
Chronic renal failure
Churg-Strauss syndrome
Ciguatera fish poisoning
Cleft lip
Cleft palate
Cloacal exstrophy
Cluster headache
Cockayne's syndrome
Coffin-Lowry syndrome
Color blindness
Colorado tick fever
Combined hyperlipidemia,...
Common cold
Common variable...
Compartment syndrome
Conductive hearing loss
Condyloma acuminatum
Cone dystrophy
Congenital adrenal...
Congenital afibrinogenemia
Congenital diaphragmatic...
Congenital erythropoietic...
Congenital facial diplegia
Congenital hypothyroidism
Congenital ichthyosis
Congenital syphilis
Congenital toxoplasmosis
Congestive heart disease
Conn's syndrome
Constitutional growth delay
Conversion disorder
Cor pulmonale
Cor triatriatum
Cornelia de Lange syndrome
Coronary heart disease
Cortical dysplasia
Corticobasal degeneration
Costello syndrome
Craniodiaphyseal dysplasia
Craniofacial dysostosis
CREST syndrome
Creutzfeldt-Jakob disease
Cri du chat
Cri du chat
Crohn's disease
Crouzon syndrome
Crow-Fukase syndrome
Cushing's syndrome
Cutaneous larva migrans
Cutis verticis gyrata
Cyclic neutropenia
Cyclic vomiting syndrome
Cystic fibrosis
Dilated cardiomyopathy
Hypertrophic cardiomyopathy
Restrictive cardiomyopathy


[List your site here Free!]

Incorporating Laboratory Values in Chronic Wound Management
From Advances in Skin & Wound Care, 9/1/04 by Hess, Cathy Thomas


To provide physicians and nurses with an overview of 3 common chronic wounds and the laboratory values that can be used to assist in accurately diagnosing them.


This continuing education activity is intended for physicians and nurses with an interest in tools that can assist in accurately diagnosing chronic wounds.


After reading the article and taking the test, the participant will be able to:

1. Describe the pathophysiology, assessment, and management of pressure, venous, and arterial ulcers.

2. Identify laboratory values that can assist in diagnosing chronic wounds.

ADV SKIN WOUND CARE 2004;17:378-86; quiz 387-8.

Wound healing is a complex process that employs specific cellular and biochemical actions to achieve wound closure. These processes-namely homeostasis, inflammation, proliferation, and maturation-occur over defined periods of time. They are often taken for granted as the wound innately granulates, contracts, and epithclializes under optimal conditions.

A wound begs the clinician's attention when the healing processes stall and the wound does not progress to closure. This type of wound is deemed chronic, and is defined as an insult or injury that has "failed to proceed through an orderly and timely process to produce anatomic and functional integrity, or proceeded through the repair process without establishing a sustained anatomic and functional result."1

Despite advancements in wound care over the last few decades, many chronic wounds continue to be affected by local and systemic factors that impair the healing process. Local factors include bacterial load and infection, trauma, edema, pressure, and moisture. Systemic factors include age; chronic medical conditions or comorbidities, such as anemia, diabetes mellitus, and renal or hepatic dysfunction; stress; medications; tissue oxygenation; and nutritional status, such as vitamin, protein, or fluid deficiencies.

Clinicians commonly evaluate and manage the typical chronic wounds, such as pressure ulcers (PrUs), vascular ulcers, and diabetic ulcers. However, many wound subsets (termed unusual wounds) mimic these common chronic wounds and add to the chronic wound population. Unusual wounds are often incorrectly assessed by clinicians, leaving the patient and the wound misdiagnosed. Examples of unusual wounds include pyoderma gangrenosum, calciphylaxis, toxic epidermal necrolysis, epidermolysis bullosa, polyarteritis nodosa, antiphospholipid antibody syndrome, cryoglobulinemia, cholesterol cmboli, disseminated intravascular coagulation/purpura fulminans, bullous pcmphigoicl, and necrotizing fasciitis.


Misdiagnosis is not unique to wound care: It can-and does-occur throughout medicine, and it is relatively common. The Web site ( reports error rates ranging from 1.4% in cancer biopsies to a high 20% to 40% in emergency or intensive care.2

Patient surveys indicate misdiagnosis rates of 8% to 40%.2 In 1997, the National Patient Safety Foundation (NPSF)3 conducted a phone survey asking patients about medical mistakes. Of the 42% of respondents who reported a medical mistake, 40% reported a "misdiagnosis or treatment error"; however, they did not separate misdiagnosis from treatment errors.

Respondents also reported that their health care provider failed to make an adequate diagnosis in 9% of cases, and 8% of people cited misdiagnosis as a primary causal factor in the medical mistake.3 Loosely interpreting these facts gives a range of 8% to 42% rate for misdiagnosis. This makes misdiagnosis one of the most common types of medical mistakes, according to

Misdiagnosis of a wound prolongs the patient's suffering by causing delayed healing; increasing the emotional and financial toll on the patient, carcgiver, and facility; and increasing medical liability. It also leads to improper medication delivery and improper topical treatments, which further exacerbates the patient's condition, covers up symptoms, prolongs the wrong diagnosis, and increases the patient's morbidity/mortality.4

This point is well illustrated in an article on skin ulcers misdiagnosed as pyodemna gangrenosum by Weening et al.4 The authors reviewed 8 years'worth of charts (240 from their facility and 157 from another facility) in which wounds were diagnosed as pyoderma gangrenosum. These diagnoses were not always correct: 10% of wounds initially diagnosed as pyoderma gangrenosum were found to be misdiagnosed for a median of 10 months. The authors concluded that misdiagnosis"exposes the patients to substantial risks associated with its treatment."4 They also said that a thorough work up is necessary to rule out diagnoses that mimic pyoderma gangrenosum.


Clinicians can reduce the chances of misdiagnosing a wound by making use of the following tools:

* the medical record, which provides a means for accurately describing the wound's characteristics at each patient visit

* risk assessment tools, which ensure systematic evaluation of individual risk factors

* nutritional risk assessment tools, which assist the clinician in understanding the strategies necessary to identify levels of nutritional risk

* manual screening tools, which include the ankle-brachial index, lower leg and foot assessments, palpation of pulses and Dopplcr ultrasound, segmental blood pressures, Semmes-Weinstein monofilament testing, transcutaneoLis oxygen pressure (TcPO^sub 2^), and vibration perception threshold assessment.

* other diagnostic tests, such as laboratory values, bacterial swab cultures, tissue cultures, skin biopsies, radiologie studies, and vascular studies, should also be taken into consideration when evaluating a patient at risk.

This article will focus on laboratory values and their role in helping the clinician avoid misdiagnosing a wound.

Laboratory values can be used to evaluate and monitor any chronic underlying medical condition, as well as to determine the patient's nutritional status.These values should be assessed on the first patient encounter to establish a baseline for care. In addition, if healing has not occurred as expected, certain laboratory values can be tracked to ensure that local and systemic factors are not contributing to poor healing. Important parameters to evaluate include protein levels, complete blood count, erythrocyte sedimentation rate, liver function tests, glucose and iron levels, total lymphocyte count, blood urea nitrogen and crcatinine levels, lipoprotcin levels, vitamin and mineral levels, and uhnalysis (Table 1). Even if only one deterrent is present, healing cannot occur.5

Tlic following is a discussion of 3 common chronic wound types-PrUs, venous ulcers, and arterial ulcers-including a detailed look at laboratory tests that can be used to assist the clinician in accurately diagnosing the wound. Note that not all laboratory tests listed would be evaluated for each patient. It remains the responsibility of the clinician to understand the patient's diagnosis, facility-specific policies and procedures related to diagnostic testing and results, and interventions used in the patient care process.



Most PrUs develop when soft tissue is compressed between a bony prominence (such as the sacrum) and an external surface (such as a mattress or the scat of a chair) for a prolonged period. Pressure, applied with great force for a short period or with less force over a longer period, disrupts blood supply to the capillary network, impedes blood flow to the surrounding tissue, and deprives tissue of oxygen and nutrients. This leads to local ischemia, hypoxia, edema, inflammation, and, ultimately, cell death. The result is a PrU.

Shear, which separates the skin from underlying tissue, and friction, which abrades the top layer of skin, also contribute to PrU development. Contributing systemic factors include infection, malnutrition, edema, obesity, emaciation, multisystem trauma, and certain circulatory and endocrine disorders.


Many patient comorbiditics have been linked to PrU devclopmcnt. Patients with the following conditions are generally accepted as having the greatest risk for PrU development:

* immobility from paralysis or other causes, such as fractures

* dehydration

* malnutrition

* problems with swallowing or chewing

* diabetes

* steroid use

* immunosuppression

* fecal incontinence

* urinary incontinence

* history of PrUs

* obesity or emaciation

* altered mental status

* infection

* respiratory insufficiency

* anemia

* cardiac problems

* muscle weakness

* neurologic problems.

Blanching erythema is an early sign that an ulcer may be forming over a bony prominence, verified by finger compression. The condition may resolve without tissue loss if pressure is reduced or eliminatcd. Nonblanchable erythema, a more serious sign, suggests that tissue destruction is imminent or has occurred.The skin may appear bright red to dark red or purple. If deep tissue damage is also present, the area may be indurated or boggy when palpated. The effectiveness of interventions and the length of time needed for healing depend on wound severity.


Successful FrU management requires a comprehensive approach. This includes taking preventive measures, relieving pressure, restoring circulation, providing appropriate nutritional and topical management, and minimizing related disorders. Clearly defined pathways and algorithms and standards of care assist the clinician in meeting this goal.

Ensuring adequate skin care, nourishment, and mobility (to relieve pressure and promote circulation) may help prevent PrUs from occurring, possibly reverse a Stage I PrU, and aid in the management of deeper PrUs.

Defined laboratory values

A number of laboratory values can be considered to assist the clinician in accurately managing a patient with a PrU. The clinician should keep in mind that many laboratory assays, such as albumin, are affected by hydration status. Laboratory tests should be repeated after a patient has been rehydrated. Careful interpretation of laboratory data is imperative, as is evaluation of current data to provide the best information on the patient's condition. If laboratory data are several months old, they will not accurately reflect the current situation.

Common laboratory tests to consider with patients diagnosed with PrUs include albumin, prealbumin, hemoglobin AlC, glucose, and complete blood count. Additional tests may be performed based on the patient's complete presentation.


Albumin is a protein that acts as a building block for cells and tissues. It is produced by the liver, and, therefore, it can be reduced in patients with liver disease. The albumin level is also diminished in patients with renal disease, malnutrition, severe bum wounds, and malabsorption syndromes. Adequate intake of protein and essential nutrients is necessary to ensure adequate production of albumin.

The albumin test is the basic screening tool for protein status and a gross indicator of nutritional status and fluid balance. It has a half-life of 18 to 20 days, making it sensitive to longterm protein deficiencies. The lower the albumin level, the greater the risk of edema because albumin accounts for a large portion of the oncotic pressure of blood plasma.

The albumin value is directly related to the severity of the protein deficiency. The extent to which albumin is decreased can help predict the risk of PrU formation. Albumin levels less than 3.2 g/dL have been shown to correlate with increased morbidity and mortality in patients admitted to the critical care unit. Elevated levels can be found in patients with dehydration, vomiting, diarrhea, and multiple myeloma.


Prcalbumin, or transthyretin, is another type of protein produced by the liver. It has a half-life of 2 to 3 days, making it a better indicator of acute nutritional status changes than albumin. The level can be diminished in patients with liver disease, widespread tissue damage, malnutrition, protein wasting, or inflammation, as well as in patients taking estrogen or an oral contraceptive.

The lower the prealbumin level, the greater the risk of mortality. Prcalbumin transports thyroxine and vitamin A throughout the body; thus, lower prealbumin levels lead to decreased transport of these substances. Hlevatcd prealbumin levels have been found in patients with Hodgkin's disease and in those taking a steroid and a nonstcroidal anti-inflammatory drug.

Hemaglobin AlC

Hemaglobin AlC (AlC) is comprised of hemoglobin A with a glucose molecule, which is attached through a process called glycosylation. It is an indicator of long-tenTi glucose control, and its value depends on the amount of serum glucose available.

AlC is mainly used as a measure of the efficacy of diabetic therapy. An elevated A1C level carries the same implications as an elevated scrum glucose level, including impaired wound healing and decreased ability to fight infection. A level above 8% increases the risk of long-term complication.


Glucose is formed from dietary carbohydrates and is stored in the liver and muscles as glycogen. A fasting blood glucose level gives the best indication of overall glucose homeostasis. Insulin allows transport of glucose into the cells for storage as glycogen. Glucagon stimulates conversion of glycogen to glucose for use by the cells as energy. Hypoglycemia results from malnutrition, cirrhosis, alcoholism, and excess insulin. The serum glucose level is elevated in patients with diabetes mcllitus, bums, crush injuries, or renal failure and in those using a steroid. A chronically elevated glucose level causes microvascular damage, which inhibits oxygen and nutrient perfusion and hampers wound healing. An elevated glucose level also affects polymorphonuclcar lymphocytes, causing decreased chcmotaxis, diapedesis, and phagocytosis, which in turn leads to a diminished ability to fight infection. Finally, an elevated glucose level is a risk factor for the development of arterial and neuropathic ulcers in patients with diabetes mellitus.

Complete blood count

A complete blood count (CBC) measures the number of red blood cells (RBCs), white blood cells (WBCs), total amount of hemoglobin in the blood, the fraction of the blood composed of RBCs (hematocrit), and the mean corpuscular volume (MCV). It also provides information about the mean corpuscular hemoglobin (MHC) and mean corpuscular hemoglobin concentration (MCHC), which are calculated from other measurements in the CBC. Tltc platelet count is usually included in the CBC.

It is important to review these blood components as they map directly to the wound healing process. For example, hcmostasis occurs immediately after initial injury. The key cell responsible for this function is the platelet, which causes the body to form a clot to prevent further bleeding. In addition, platelets also release key cytokincs, such as platelet-derived growth factor, that call in cells to participate in later phases of healing. Without the proper platelet count, wound healing is delayed.

These and other tests, such as renal and liver function tests and electrolyte levels, should be monitored based on the care plan related to the clinical presentation of the patient and the wound.



Chronic venous insufficiency (CVI) is the result of deep vein obstruction, incompetent venous valves, and/or inadequate calf muscle function. Partial or complete deep vein obstruction may occur from thrombosis, scar tissue, obesity, pregnancy, or malignancy. Valves maybe incompetent due to lower leg trauma, deep vein thrombosis, or congenital anomalies. Poor calf muscle function may be secondary to paralysis, decreased ankle joint mobility (as seen with fractures or arthritis), decreased activity, or muscle atrophy. Abnormalities in the veins, valves, and/or calf muscle result in impaired venous return and abnormally high venous pressure, both at rest and with ambulation. This leads to edema and altered microcirculation in the skin, which results in impaired healing.

Venous ulcers typically occur superior to the medial malleolus (near the saphcnous vein) or within the lower third of the calf. The wound is generally ruddy or red in appearance; the surrounding skin may exhibit venous dilation, including submalleolar venous flare (typical of venous insufficiency), telangiectasias, reticular veins, varicose veins, edema (typical of more advanced venous disease), atrophie blanche, maceration, hypcrpigmcntation (from hemosidehn staining), and lipodcrmatosclerosis. Scarring from prior healed ulcers may be noted, rtin has been reported as nonexistent to severe and, constant. Generally, pain is present with leg dependence (sitting and standing) and is reduced with leg elevation.

Venous ulcers are frequently precipitated by trauma. The patient may have traumatized the leg weeks to months before the wound appeared. In some cases, the patient reports a previous pruritic rash (stasis dermatitis) or indicates that the ulcer developed after the skin was scratched. A spontaneous blister may form in the presence of severe edema, and following rupture, may result in a chronic wound. Once the wound occurs, the high venous pressure and resulting edema interferes with healing.


Compression therapy remains the cornerstone of venous ulcer management. Compression has been shown to improve the rate of ulcer healing, reduce the incidence of recurrence, and prolong the time to first recurrence. Between 50% and 60% of patients heal with compression therapy alone within 6 months. Physiologic changes that have been reported to occur using compression therapy include improvement of lymphatic drainage, reduction of superficial venous pressure, improvement of blood flow velocity through unoccluded deep and superficial veins, and reduction of reflux in the deep veins. A venous ulcer that demonstrates healing after 4 weeks of compression therapy is likely to be completely healed by 24 weeks, according to studies. If the wound does not show healing after 4 weeks of compression therapy, it tends to remain problematic.

Defined laboratory values

To accurately manage the patient with a venous ulcer, the clinician should obtain nutritional laboratory values (as previously discussed), as well as a CBC.


Protein is responsible for the growth and maintenance of tissue, fluid balance, and antibody andT-cell formation, as well as for hormone and enzyme production. It can be influenced by various factors, such as diminished dietary intake; decreased protein production; increased metabolic rate; or excessive loss through the skin, kidney, or gastrointestinal (CI) tract. In addition, the protein level can be affected by stress, hormones, infection, and organ dysfunction. Therefore, it is not a specific indicator of nutritional status. Total protein is primarily comprised of albumin and globulin.

The presence of a wound and the body's attempt to heal it may increase the patient's baseline metabolic rate. The liver catabolizcs protein to support the wound's increased demands on the body. If the patient does not consume enough protein to compensate for the increased catabolism, protein deficiency results.

Protein deficiency impedes wound healing for various reasons, such as a reduced ability to repair the wound and to fight infection. The negative effect on wound repair is related to the subsequent decrease in DNA production, ncovascularization, Bbroblast proliferation, collagen synthesis, and wound remodeling. Weakened resistance to infection is caused by decreased antibody and complement production, leukocyte phagocytosis and intracellular killing, and macrophage phagocytosis.

Edema is another result of protein deficiency, which subsequently decreases tissue oxygenation and nutrient transport to the wound. In addition, thymic atrophy occurs secondary to decreased thymic hormone secretion, which leads to decreased T-lymphocyte production.

Total lymphocyte count

Lymphocytes are part of the immune system. T-lymphocytes, which develop in the thymus, are involved in cell-mediated immunity, such as bacterial death and tumor immunity. Blymphocytes develop in the bone marrow and are responsible for humoral immunity. They synthesize immunoglobulins, which react to specific antigens.

Measurement of lymphocytes aids in the diagnosis of immunosuppression and autoimmunity. A decrease in the total lymphocyte count (indicating impaired immunity) can result from decreased protein intake. The lower the count, the higher the risk of morbidity and mortality. A decreased total lymphocyte count has also been associated with surgery, lupus, lymphoma, malnutrition, immunodeficiency, and the use of immunosupprcssants. An increased total lymphocyte count has been associated with alcohol use, smoking, and autoimmune disorders.

Blood urea nitrogen

Urea is a byproduct of protein metabolism and is excreted by the kidneys. Blood urea nitrogen (BUN) is an indicator of renal function and fluid status. Men usually have a slightly higher BUN level than women.

Elevated urea levels (uremia) have been associated with delayed wound healing. Causes of uremia include Gl bleeding; prcrenal failure due to reduced blood flow to the kidneys or crush injuries; intrinsic renal failure due to glomerulonephritis or nephrotic syndrome; postrenal failure due to obstruction of me ureter or urethra by stones or tumor; and use of nephrotoxic drugs (such as cyclosporin), diuretics, certain antibiotics, or salicylatcs.

Concurrently elevated levels of BUN and crentinine suggest kidney disease, whereas an elevated BUN level alone may indicate dehydration or a breakdown of blood products in the Gl tract that may occur with intestinal bleeding. With declining renal function, doses of certain medications and antibiotics should be decreased to avoid toxic buildup. Hlectrolyte abnormalities can occur with worsening renal function. Decreased urea levels result from ovcrhydration, liver damage, malnutri tion, and phcnothiazide use. Ritients should ingest 30 to 35 mL/kg of fluids, preferably water, daily.

Liver function tests

Liver function tests measure the enzymes alanine aminotrans ferasc (AlJl), aspartate aminotransferase (AST), and alkaline phosphatasc. These enzymes are produced by liver cells and are effective for diagnosing liver dysfunction.The transaminases, AST and ALT, catalyze the transfer of an amino group between an amino acid and an alpha-keto acid, which aids in the production of amino acids for protein synthesis in the liver. AIT is found almost exclusively in the liver, whereas AST ran also be found in skeletal muscle, the kidneys, and the brain. Alkaline phosphatasc is an enzyme produced in the liver and bones.

Extreme elevations in AIT and AST levels are characteristic of acute hepatitis; mild elevations are indicative ot chronic liver disease, commonly caused by medications or chronic hepatitis. The longer the duration of liver disease, the more likely that liver failure or cirrhosis is imminent. If the ALF level is more markedly elevated than the AST level, acute hepatitis or liver necrosis is likely. However, an AST level greater than an AlT level suggests chronic hepatitis, cirrhosis, or myocardial necrosis. The alkaline phos phatase level is significantly elevated in acute hepatitis, with slight Iy elevated levels characterizing chronic disease. Itigct's disease, fractures, rheumatoid arthritis, and bone malignancy also lead to elevated levels. Malnutrition, hypothyroidism, and vitamin C deficicncy can cause decreased alkaline phosphatasc level. 'Hie more severe and longer the insult to the liver, the greater the decrease in alkaline phosphatase production. This liver dysfunction can also lead to toxic levels of certain antibiotics, which are metabolized through the liver.


Hemoglobin, a protein, gives blood its red color. It is comprised of a protein globin envelope and hcme, which binds and transports oxygen through the use of iron. Any deficiency of vitamins, minerals, or amino acids can cause decreased hemoglobin production.

The lower the hemoglobin level, the less oxygen is transported to tissues, and the less capacity wounds have to heal properly. Oxygen plays a role in enzymatic and cellular metabolic reactions necessary for cell growth and proliferation. A decreased hemoglobin level can result from anemia, cirrhosis, hemorrhage, renal disease, volume overload, or from the use of certain medications (such as penicillin, tetracycline, aspirin, sulfonamides, indomethacin, and vitamin A). An artificially low level of hemoglobin occurs when blood is drawn from the same arm through which intravenous (I.V.) fluids are being given. A truly decreased hemoglobin level is a risk factor for PrU formation. An increased hemoglobin level can result from dehydration, polycythcmia, severe burns, exposure to high altitudes, and use of gcntamicin.


Hematocrit is the volume of packed RBCs in 100 mL of blood; that is, it represents the concentration of red cells in blood. Decreased hematocrit has a direct effect on wound healing and is associated with blood loss, anemia, malignancies, protein malnutrition, liver and renal disease, lupus and rheumatoid arthritis, and the use of antincoplastic drugs and penicillin. Elevated hematocrit can result from dehydration, diarrhea, polycythemia, or bums. As with the hemoglobin level, an artificially low hematocrit can occur if blood is drawn from the same arm through which I.V. fluids are being given.

Additional tests to consider when evaluating a patient with venous insufficiency include venography, Doppler ultrasound, anklc-brachial index, plethysmography, and tissue biopsy.



Arterial insufficiency refers to impairment of arterial blood flow leading to tissue ischemia and, potentially, necrosis. Such impairment can occur acutely (eg, trauma, thrombosis) or chronically (eg, atherosclerosis). Both acute and chronic arterial insufficiency can lead to lower extremity ulcers. Arterial insufficiency can occur at any level, from large arteries to arterioles and capillaries. Tissue ischemia that leads to leg ulcers tends to occur more as large vessel or mixed disease.

Obstruction of arterial flow can be classified as "anatomic" or "functional."Anatomic causes of obstruction include thrombosis, emboli, atherosclerosis, and vasculitis. Functional impairment occurs with conditions such as Raynaud's disease, where abnormal vasomotor function leads to reversible obstruction. Reversible ischemia tends to cause pain, and infrequently results in ulceration. Aside from obstruction, other potential causes of impaired arterial flow include disruption (eg, trauma), fistulas, and aneurysms.

Ischemic ulcers tend to have a punchcd-out appearance; they are small, round, and have smooth, well-demarcated borders.The wound base is typically pale and lacks granulation tissue. Wet or dry necrotic tissue may be present. Arterial ulcers tend to occur over the distal part of the leg, especially the lateral malleoli, dorsum of the feet, and the toes. They can be shallow or deep, and are frequently painful. Typically, the patient complains of pain when the feet are elevated, especially at night, and states that the pain is reduced with leg dependence.

In addition to these common features, the physical examination may reveal a decrease in peripheral pulses; lack of hair over the distal leg; and cyanosis, pallor, and/or atrophy of the surrounding skin. Lifting the leg greater than 60 degrees can induce pallor in the ischemic limb. When dropped to a dependent position, the limb may become red (dependent rubor).


Revascularization is the key to the treatment of arterial ulcers secondary to peripheral arterial disease (FAD). Other measures may include topical therapy, conservative dcbridcmcnt, and pain control. Treatment is also directed at the pathogenic causes of arterial disease. For example, management of atherosclerosis includes exercise therapy, cholesterol reduction, smoking cessation, and control of blood pressure and blood glucose. Anuplatelet agents (aspirin, Udopidine, clopidogrel) and xanthine derivatives (pentoxifylline) are commonly used to treat the symptoms associated with PAD. However, medical treatment alone has typically been of limited effectiveness for treatment of arterial ulcers. Newer modalities, including human growth factors and bioengineered skin substitutes, hold significant promise in the treatment of these frequently difficult-to-heal wounds.

Defined laboratory values

To accurately manage the patient with an arterial ulcer, the clinician should obtain the following laboratory values: glucose, lipids, CBC, eosinophils, cryoglobulins, antiphospholipid antibodies, antinuclear antibody panel, and rheumatoid factor. The laboratory tests, in tandem with diagnostic tests, assist the clinician in making a more accurate and specific arterial diagnosis.


As previously discussed, a chronically elevated glucose level causes microvascular damage, which inhibits oxygen and nutrient perfusion and hampers wound healing. An elevated glucose level also affects polymorphonuclear lymphocytes, causing decreased chemotaxis, diapedesis, and phagocytosis, which in turn leads to a decreased ability to fight infection. An elevated glucose level is a risk factor for arterial and neuropathic ulcers in patients with diabetes mellitus.


Lipoproteins, such as cholesterol and triglycerides, are lipids bound to protein; they are absorbed in the intestines. Cholesterol is an important component of cell membranes, bile acid, and steroid hormone synthesis. Triglycerides are manufactured by the liver and provide energy to the heart and muscles. They are transported in blood as chylomicrons.

Hyperlipidemia is a risk factor for peripheral arterial disease and subsequent ischemic ulcer formation. Elevated cholesterol levels are associated with diabetes mellitus, hypothyroidism, atherosclerosis, excess dietary intake of cholesterol, renal failure, alcoholism, familial hyperlipidemia, and the use of certain medications (aspirin, steroids, sulfonamides, vitamins A and D, and oral contraceptives). Artificially elevated levels can result from food consumption 12 hours before obtaining the blood specimen. Decreased levels can be found in the presence of malnutrition; infection; hyperthyroidism; malabsorption; anemia; inflammation; and the use of neomycin, hypoglycemies, estrogens, and tetracycline.

Decreased triglyceride levels are found in hyperthyroidism, protein malnutrition, vitamin C excess, and use of metformin. Increased levels occur in hypothyroidism, nephritic syndrome, atherosclerosis, cirrhosis, diabetes, hypertension, excess dietary intake of triglycerides, alcoholism, familial hyperlipidemia, and oral contraceptive use. Artificially elevated levels can occur if patients do not fast for 12 hours before having a blood specimen drawn.


Cryoglobulins are abnormal immunoglobulins. At temperatures below normal body temperature (98.6° P [37° C]), cryogloblins no longer stay suspended in the blood. They precipitate out, forming complexes that can block small blood vessels, especially in the face and hands. Although a positive cryoglobulin test that is properly performed can confirm the diagnosis of cryoglobulinemia, patients could also have concomitant arterial disease. If arterial disease is suspected, a further workup may be indicated.

Antiphospholipid antibodies

Antiphospholipid antibody syndrome, also known as Hughes-Stovin syndrome, is a disorder characterized by the presence of multiple antibodies (lupus and anticoagulant and anticardiolipin antibodies) that are associated with both arterial and venous thrombosis (clots). There are two main classifications of the antiphospholipid antibody syndrome, another unusual wound subset. A patient with an underlying autoimmune disorder, such as systemic lupus erythematosus, is said to have secondary antiphospholipid antibody syndrome. A patient with no known underlying autoimmune disorder has primary antiphospholipid antibody syndrome. Antiphospholipid syndrome can present with ulcers similar in appearance to ischemic arterial ulcers. Therefore, if antiphospholipid antibody syndrome is suspected, these tests should be ordered.

Antinuclear antibody panel (ANA)

This test looks for the presence of antibodies that target components of a cell nucleus. An ANA test may be ordered to aid in the diagnosis of autoimmune conditions, such as systemic lupus erythematosus (SLE) and drug-induced lupus, scleroderma, Sjögren's syndrome, Raynaud's disease, juvenile chronic arthritis, rheumatoid arthritis, antiphospholipid antibody syndrome, autoimmune hepatitis, and many other autoimmune and nonautoimmune diseases. ANA can assist the clinician in positively determining which autoimmune disease has developed.

Rheumatoid factor (RF)

RF is an antibody that attaches to a substance in the body called immunoglobulin G (IgG), forming a molecule known as an immune complex. This immune complex can activate various inflammatory processes in the body. These findings can assist the clinician in determining the presence of an inflammatory process, such as rheumatioid arthrutis. A positive RF test does not definitively rule out arterial causes for an ulcer.

Diagnostic tests

Additional diagnostic tests can be performed to assist in accurately diagnosing the patient's wound.


Angiography is considered the gold standard for diagnosing arterial vascular disease. This procedure is indicated for patients who are candidates for revascularization procedures. The test has associated risks, including cholesterol plaque embolization, acute avascular occlusion, arterial damage, and contrast induced nephropathy.

Magnetic resonance angiography (MRA)

MRA is a noninvasive test to determine the presence and severity of arterial obstruction, such as PAD.

TcPO^sub 2^

Transcutaneous oxygen measurement can assess for the presence of microvascular insufficiency. A measurement greater than 30 mm Hg indicates adequate perfusion; a value less than 20 mm Hg indicates disease. If the tissue surrounding an ulcer has a TcPO^sub 2^ less than 20 mm Hg the wound typically will not heal.


Diagnosing a specific wound type is a complex process. It takes accurate wound and skin assessment skill sets, including understanding the physical findings of the wound and skin, evaluating the patient's laboratory values and diagnostic tests, assessing nutritional needs, and selecting appropriate management modalities (eg, topical dressings or drugs, support surface products, and off-loading devices). An accurate plan of care is important for successful wound healing.

Remember, the clinical goal when evaluating a patient is confirmation of the diagnosis. Understanding the laboratory values and diagnostic tests that support the diagnosis, is critical. No single assessment parameter confirms a diagnosis. Careful review of the patient's wound history, laboratory findings, diagnostic tests, and management modalities will support or place doubt on a tentative diagnosis that is based solely on case history data and clinical findings.


1. Lazarus GS, Cooper DM, Knighton DR et al. Definitions and guidelines for assessment of wounds and evaluation of healing. Arch Dematol 1994; 130:489-93.

2. "How common is misdiagnosis?" 2004. Available online at http://; accessed July 6, 2004.

3. National Patient Safety Foundation. Public opinion of patient safety issues: research findings; 1997. Available online at; accessed June 11, 2004.

4. Weenig RH, Davis MDP, Dahl PR, Su WPD. Skin ulcers misdiagnosed as pyoderma gangrenosum. N Engl J Med 2002;347:1412-8.

Cathy Thomas Hess, BSN, RN, CWOCN * President and Director of Clinical Operations * Wound Care Strategies, Inc * Harrisburg, PA * Clinical Consultant * Advances in Skin & Wound Care * Ambler, PA

Jennifer T. Trent, MD * Resident * Department of Dermatology and Cutaneous Surgery * University of Miami School of Medicine * Miami, FL

The authors have disclosed that they have no significant relationships or financial interests in any commercial companies that pertain to this education activity.

Copyright Springhouse Corporation Sep 2004
Provided by ProQuest Information and Learning Company. All rights Reserved

Return to Cryoglobulinemia
Home Contact Resources Exchange Links ebay