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CE: Assessment of Red Blood Cell and Coagulation Laboratory Data

Source:

AACN Advanced Critical Care

October/December 2004, Volume :15 Number 4 , page 622 - 637 [Free]

Keywords

anemia, coagulation, hematology, hemolysis, laboratory data

 

Authors

  1. Rempher, Kenneth J. MS, RN, MBA, CCRN, ACNP-CS
  2. Little, Jean BSN, RN

Abstract

Critically ill patients present with a myriad of hematologic problems of various etiologies. The astute advanced practice nurse carefully reviews laboratory data incorporating principles of diagnostic reasoning and critical thinking while developing the plan of care. An in-depth understanding of hematology including red blood cells, red blood cell indices, and coagulation laboratory data is essential in the quest to understand the patient's pathophysiology.

 

With every decade, nurses and physicians learn more about diseases that have plagued mankind for centuries-learning in greater detail about the deleterious effects and subsequent outcomes that often begin as subtle changes in traditional laboratory data. Greater focus on interpreting hematologic data and seeking support for diagnoses in clinical correlates will serve nurses well.

 

This article intends to move advanced practice nurses beyond their current understanding of hematologic values-enabling them to understand that how and why we measure is as important as what we measure. No longer is it enough to simply measure physiologic data to develop a care plan driven by the patient's diagnoses. The contemporary nurse understands the importance of assigning meaning to data. Meaningful data are manageable data.

 

Article Content

Proper hematologic and immunologic assessment of critically ill patients requires not only that the advanced practice nurse (APN) be adept at identifying deviations from normal values, but also that the APN be able to interpret the deviations, use the information to develop an effective plan of care. Specifically, it is within the domain of advanced practice nursing to combine data gleaned from a variety of sources, including physical exam, laboratory exam, and patient interview, in an effort to form a diagnosis. Furthermore, as more information about disease and the way patients respond to disease becomes available through laboratory data, it is imperative that nurses in advanced practice roles have a full and detailed understanding of routine laboratory values. A grounded understanding of laboratory data is imperative as APNs serve not only their patients, but also other nurses who turn to APNs for guidance and information. This article provides information that will augment the clinical and diagnostic skills of both direct care providers and those who oversee the delivery of nursing care.

 

Units of Measurement

Laboratories in the United States tend to report data using a version of the metric system that expresses values in mass per unit volume. In contrast, most other countries report data in moles per unit volume which is consistent with the Systeme Internationale (SI) adopted by the General Conference on Weights and Measures in 1960. Because mass per mole varies with the molecular weight of the analyte, conversion between the system used in the United States (American Units) and the SI system requires different conversion factors. The difference between the two systems is most greatly appreciated in the interpretation of chemical concentrations.

 

Issues Associated With Interpretation of Hematologic and Immunologic Data

Seven percent of a healthy adult's body weight is comprised of blood plasma and its cellular contents including red blood cells (RBCs, erythrocytes), white blood cells (WBCs, leukocytes), and platelets (thrombocytes). 1 Blood volume is composed of 55% plasma, 45% RBCs, and 1% WBCs and platelets. Collectively, these elements constitute the blood and serve as significant and sensitive indicators of a patient's health status. The importance of accurately interpreting these sensitive indicators of health requires that APNs understand the potential influence of other variables that may possibly confound results.

 

Certain generic conditions exist that can impact interpretation and ultimately the diagnostic reasoning used to arrive at clinical decisions and therapeutics. Because abnormal results are defined in terms of deviation from a normal range of values, it is important to understand how "normal" is derived.

 

The term "normal," as it relates to laboratory values, should be conceptualized as a statistical term that defines a range within which 95% of the population's values fall. A range is established by calculating the mean value for a healthy group of individuals and reporting a reference range as the mean +/-2 standard deviations. Clinicians must understand that approximately 5% of normal patients will fall beyond the limits of the reference range. The blurred line between normal and abnormal requires the prudent clinician to exercise caution when interpreting laboratory values that fall outside of the defined range. Relating laboratory data to the patient's physical state will prevent overreaction to mild abnormalities in the absence of clinical correlates.

 

Other factors must be considered when evaluating laboratory values. Preanalytical variation, defined as variation associated with conditions of testing, includes factors such as patient preparation, positioning, type of sample, (venous or capillary), type of collection tube used, and specimen transport and storage. 2-5 Specific examples of preanalytical causes of variation include leaving the tourniquet on too long and varying amounts of anticoagulant in collection tubes. When analyzing hematologic values, it is imperative that the clinician knows the vascular source of the specimen. In a classic study of preanalytical factors contributing to lab variation, Daae et al 3 found that hematologic parameters obtained from healthy adults demonstrated a 32% decrease in platelet counts, 10% increase in hemoglobin levels, and a nearly 23% increase in WBC counts in capillary versus venous samples. Preanalytical variation may also include physiologic variables such as age, gender, circadian rhythm, and lifestyle habits including exercise, smoking, and alcohol consumption. 6

 

Analytical variation, defined as variation in outcomes resulting from the mechanics of testing, has become a relatively minor cause of overall laboratory variation with the advent on modern, fully automated analyzers. 4,5

 

Interindividual and intraindividual subtypes comprise the more general category, biologic variation. Defined as variation in a patient's test results over time relative to a group mean (interindividual) or the patient's own mean (intraindividual), biologic variation is often to blame for unanticipated discrepant results in serial testing. 2 Interindividual variation is influenced by multiple demographic variables including the patient's age, sex, and race. Other common influencing and variable factors across populations that impact interindividual variation include pregnancy and smoking history. Trends in intraindividual variation tend to be less significant but can occur within the same day or from one day to another, often depending upon diurnal patterns. 2 For example: hemoglobin and hematocrit are typically highest in the evening when tested serially, while mean leukocyte counts tend to be highest in the afternoon. There is no diurnal variation in RBCs.

 

Red Blood Cells (Erythrocytes)

RBCs are approximately 7 [mu]m in diameter and contain hemoglobin which combines with oxygen (O2) to form oxyhemoglobin. The RBC originates from the pluripotent stem cell under the influence of the hematopoietic growth factor erythropoetin. 1 The normal RBC count in males is 4.6 to 6.2 x 106 cells/mm3 and 4.2 to 5.4 x 106 cells/mm3 in females (Table 1). Various gender-associated factors including menstruation in women and the presence of androgens in men, contribute to the differing normal ranges. 1,7 Increases in the RBC count may be the result of either absolute primary polycythemia (polycythemia vera) or secondary polycythemia (hypoxemia of lung or cardiovascular disease, increased erythropoietin production associated with renal cyst, renal cell carcinoma, cerebellar hemangioblastoma, or high O2 affinity hemoglobinopathy). A special type of secondary polycythemia, known as stress polycythemia, is caused by hemoconcentration associated with exercise, obesity, exertion, and anxiety, and also causes the RBC count to increase. RBC count is normally higher in individuals residing at high altitudes secondary to decreases in the partial pressure of atmospheric oxygen. The increase in overall RBC production serves as a compensatory mechanism intended to ensure adequate tissue perfusion. Relative increases in RBCs occur with dehydration (Table 1).

  
Table 1 - Click to enlarge in new window Red Cell and Red Cell Indices: Normal Values

Reduction in RBCs can also be absolute or relative in nature. Absolute causes of decreased RBCs include loss by bleeding or hemolysis (intravascular or extravascular), or failure of marrow production (due to a broad variety of causes). Blood loss can be external or internal in origin. External loss is associated with injuries including traumatic amputations and partial amputations. 8 Internal bleeding occurs through multiple mechanisms including massive hemothorax, retroperitoneal injury (hip fracture, renal laceration, great vessel tear), or intraperitoneal injury (eg, liver, spleen, major vessel laceration). 9 Relative reductions in RBCs occur in overhydration (Table 1).

 

Hemolysis can be either intravascular or extravascular. Intravascular hemolysis implies the destruction of the RBC within the blood vessel. 1 It is caused by mechanical trauma (burns, disseminated intravascular coagulation), complement fixation (transfusion reaction), and the presence of soluble toxic substances in the RBC's delicate environment (ie, intravenous administration of distilled water) (Table 1). At the cellular level, intravascular hemolysis causes RBC's to become fragmented, thus becoming schistocytes. At some point, hemoglobin is released from the schistocytes, allowing it to freely flow in the plasma until it binds to the protein haptoglobin. The hemoglobin/haptoglobin complex is transported to the liver where it is ultimately metabolized to bilirubin by hepatic reticuloendothelial cells and excreted in the bile. 1 Hemoglobin/haptoglobin activity can be assessed with a haptoglobin blood test. While haptoglobin blood tests are used in aiding the diagnosis of hemolytic anemia, it is an acute phase reactant and should not be used independently in assessment of hemolysis. 1 Various conditions can cause haptoglobin levels to be abnormal. A discussion of such conditions is beyond the scope of this article; the reader is referred to a clinical laboratory textbook for further information.

 

In patients with severe intravascular hemolysis, consumptive deficiencies in haptoglobin may cause the accumulation of hemoglobin in the plasma. Hemopexin, an additional protein suited to transport hemoglobin to the liver may be activated in the absence of sufficient haptoglobin but this, too, may become deficient in severe cases. In the case where free hemoglobin is devoid of either transport protein, it will either be removed directly by the liver, or will be dissociated into dimers small enough to pass through the glomerulus. 1 Ultimately, the filtered hemoglobin will be reabsorbed in the proximal renal tubules. At such time that the rate of filtration exceeds the rate of absorption, the clinician will be able to detect free hemoglobin in the urine, also known as hemoglobinuria. The presence of free hemoglobin in the urine serves as a sign of severe intravascular hemolysis and requires immediate attention. Lactic dehydrogenase is also typically elevated in patients with intravascular hemolysis.

 

Extravascular hemolysis, more common than intravascular hemolysis, occurs when premature RBCs are phagocytized by macrophages in the liver and spleen. Causes include RBC membrane abnormalities such as bound immunoglobulin, Rh incompatibility, or physical abnormalities restricting RBC deformability preventing egress from the spleen. 1 Extravascular hemolysis is characterized by spherocytes-abnormally round erythrocytes with dense hemoglobin content. It is unlikely that haptoglobin will be decreased in cases of extravascular hemolysis, as the free hemoglobin is not circulating in the plasma.

 

Blood dyscrasias including hemophilia or those associated with malignancy are also implicated in abnormally low RBC counts secondary to loss by bleeding (Table 1). Relative causes of reduced RBC counts include intravascular dilution secondary to overhydration (ie, intravenous fluids).

 

Reticulocytes

Reticulocytes are immature RBCs that have matured from the nucleated normoblast stage retaining some residual RNA and mitochondria but no nucleus. 1 The reticulocyte count (retic count) serves as an index of mature RBC production by the bone marrow. Normal values range from 0.5 to 1.5% for males and 0.5 to 2.5% for females (Table 1). Absolute reticulocyte concentration is calculated by multiplying the percent reticulocytes by the RBC count. Elevated reticulocyte counts are appreciated in patients whose condition requires accelerated RBC production. The reticulocytes replace lost, destroyed, or malfunctioning RBCs. In addition, reticulocyte counts will be elevated in a variety of anemias. In the presence of a low hemoglobin state, the bone marrow is able to increase production of RBCs three-fold. 10 This increase in reticulocyte production with the subsequent increase in RBCs constitutes (in part) hyperproliferative anemia. However, increased production requires adequate stem and progenitor cells, sufficient nutrients, and adequate amounts of erythropoietin. 10 Erythropoetin is produced in the kidney by the epithelial cells of the proximal tubule and endothelial cells. 11

 

Clinicians should be wary of elevated reticulocyte counts in the presence of an otherwise normal complete blood count as this is indicative of polycythemia vera. 12 Polycythemia vera (PV) is a stem cell disorder characterized as a panhyperplastic, malignant, and neoplastic marrow disorder. The condition presents with an elevated absolute RBC mass due to uncontrolled red cell production and concomitant increases in both WBC (myeloid) and platelet (megakaryocytic) production. Overproduction of the blood cells is secondary to an abnormal clone of the hematopoietic stem cells. 13

 

Certain conditions, including poor nutrition and intrinsically impaired bone marrow (primary bone marrow disorder), may cause low reticulocyte counts. This condition, hypoproliferative anemia, is a subset of normocytic anemias. 10

 

Hemoglobin and Hematocrit

Hemoglobin assessment is a routine part of clinical practice. Hemoglobin is a critical protein contained in erythrocytes and facilitates transfer of oxygen and carbon dioxide across the alveolar membrane in the lungs. Various preanalytical factors, including age, gender, race, and geographic location, are known to influence normal values. Normal values for males range from 13 g/dL to 18 g/dL and from 12 g/dL to 16 g/dL for females (Table 1). 12 Hemoglobin levels for Caucasians are slightly higher by 0.7 g/dL. 2 Overhydration causing dilution of intravascular volume, blood loss, and anemia will all cause decreased hemoglobin values. Conversely, dehydration (contraction of the intravascular space), adaptation to high altitudes, chronic hypoxia, and polycythemia vera all cause increases in hemoglobin. 12

 

Hematocrit is defined as the packed cell volume (PCV) of a blood sample representing the percentage of erythrocyte mass in a 100 mL sample of whole blood. 12 While hematocrit is clearly dependent upon the quantity of erythrocytes, it is also influenced by the RBC's size. Hematocrit values are diminished in the presence of many of the same conditions known to decrease hemoglobin. Likewise, factors know to increase hemoglobin will also increase hematocrit. To ensure that reported values for hemoglobin and hematocrit are correct (they are usually reported together), one can use the "rule of three" as a mathematical check. In patients who are normocytic and have normochromic RBCs, multiplying the hemoglobin by 3 will equal the hematocrit. Deviations in the calculated value beyond +/- 3% of the measured hematocrit laboratory value could reflect either instrument error or a pathological problem that requires attention. 2 Normal hematocrit values range from 45 to 54% for males, and 36 to 46% for females (Table 1). 12

 

Red Cell Distribution Width

Red cell distribution width (RDW) is a derived measure of RBC homogeneity. RDW is also, in combination with the mean corpuscular volume (MCV), often defined as a measure of RBC size variation (anisocytosis). 1 Large (wide) RDW values reflect samples with significantly heterogeneous cell sizes and small (narrow) RDW values reflect a sample with a relatively tight range of cell sizes. The RDW is useful in the differential diagnosis of microcytic anemias. The normal RDW range is 11.5 to 14.5% (Table 1). 1 While the RDW is highly sensitive, its function as a clinical marker is limited by its low specificity. However, RDW is helpful in distinguishing thalessemia from iron deficiency anemia. 14 A large (wide) RDW is associated with iron deficiency anemia while a small (narrow) RDW is most often associated with thalessemia.

 

Anemias

A discussion of RBCs and RBC indices would not be complete without some mention of anemias. While multiple other laboratory values including total iron binding capacity (TIBC) and ferritin contribute to the assessment and diagnosis of anemia, the scope of this discussion will examine the influence of RBC and RBC indices in creating anemic states.

 

Anemia has been described as the most common hematologic disorder. 15 Nearly 95% of patients admitted to critical care units have low hemoglobin values by day 3 of the critical care stay. 16 Although recent data suggest that hemoglobin levels as low as 7 g/dL are well tolerated by critically ill patients, many prescribers continue to order transfusions at this level and even higher levels. 17 The diagnosis and treatment of anemia in critically ill patients is a fundamental clinical skill in advanced practice nursing.

 

Anemia is typically defined by low hemoglobin and hematocrit but the pathogenesis lies in diminished erythropoetin production in response to physiologic stimuli, alterations of iron metabolism, and bone marrow suppression. 18 Significant decreases in hemoglobin concentration result in decreased O2 carrying capacity. However, a paradoxical improvement in O2-carrying capacity has been described in the presence of moderate decreases in hematocrit. 18 The improvement in oxygenation is attributed to the enhanced microvascular perfusion facilitated by decreased blood viscosity.

 

Anemias are classified morphologically based on the average size, weight, and hemoglobin concentration of the erythrocytes. Various causes of anemia are known to produce specific sizes of erythrocytes. Hence, the aforementioned indices were developed to assist with the diagnosis of the various types of anemias. The general categories of morphologic classification include macrocytic, normochromic; normocytic, normochromic; and microcytic, hypochromic.

 

Erythrocyte Indices

In 1929, Maxwell Winetrobe introduced erythrocyte indices as a mechanism for describing the size, weight, and hemoglobin concentration of individual RBCs. Indices are used primarily in the diagnosis and classification of anemias. All indices are calculated using the erythrocyte count, hemoglobin concentration, and hematocrit. Mean cell volume (MCV) is a measurement of RBC size as it relates to the hematocrit. RBCs of larger than normal size (macrocytes) hold greater volume individually and collectively, subsequently increasing the hematocrit (defined earlier as the "packed cell volume"). MCV is calculated by dividing the hematocrit by the RBC count. RBCs with smaller than normal volume are described as microcytes. Both thalessemia minor and iron deficiency anemia are microcytic conditions. 2 Patients diagnosed with pernicious anemia, folic acid anemia, chronic liver disease, myelodysplastic syndrome, and chronic alcoholism will often present with macrocytic RBCs. 15 The normal range of MCV values for both males and females is 81 to 98 [mu]mm3 (Table 1). 12

 

The mean cell hemoglobin (MCH) is a measure of RBC weight and is calculated by dividing the hemoglobin by the RBC count. Decreased MCH values are seen in hypochromic and microcytic anemias. 12 Types of microcytic anemia include heterozygous thalassemia and anemia of chronic disease (Table 2). 19 Increased MCH values are seen in patients with macrocytic anemias. Normal MCH values run 27 to 32 pg/RBC for both males and females (Table 1). 12 Examples of macrocytic anemias include pernicious anemia and folic acid deficiency (Table 2). The remaining index, mean cell hemoglobin concentration (MCHC), is calculated by dividing the hemoglobin by the hematocrit. The MCHC reflects the mean concentration of hemoglobin in the average RBC. Decreased MCHC values are noted in patients diagnosed with iron deficiency anemia and thalessemia, while increased values are seen in patients suffering from intravascular hemolysis. 12 The normal range for MCHC is 32 to 36% (Table 1). 12

  
Table 2 - Click to enlarge in new window Index Characteristics of Select Macrocytic and Microcytic Anemias

Erythrocyte Sedimentation Rate

The aggregation of erythrocytes is greatly influenced by electrostatic forces. Erythrocytes normally have net negative ionic charges and, therefore, repel each other. However, in the presence of positively charged, high molecular weight proteins (eg, fibrinogen, immunoglobulins), the RBCs aggregate, causing them to fall (settle) more quickly, subsequently increasing the sedimentation rate. The erythrocyte sedimentation rate (ESR), also known as the "sed" rate, is defined as the distance in millimeters that RBCs fall after standing for 1 hour in a specially calibrated tube of anticoagulated blood. The results are expressed as mm/hour and represent the millimeters of clear plasma present at the top of the column in the tube. Settling of RBCs is dependent upon four factors: (1) RBC morphology, (2) the concentration of RBCs, (3) fluid status, (4) protein composition of the plasma. 2 Normal values for ESR are gender and age specific. The rate in males is 0 to 10 mm/hr and in females, 0 to 20 mm/hr. Rates in older males are increased to 15 to 20 mm/hr, and in older females, normal rates are 20 to 30 mm/hr. 20

 

Although nonspecific and nondiagnostic, ESR is used to demonstrate the presence of inflammation and/or tissue destruction. Inflammatory diseases including tuberculosis, acute infection, multiple myeloma, inflammatory bowel disease, and rheumatic fever cause increases in ESR. 20 Tissue necrosis resulting from traumatic injury and acute myocardial infarction as well as pregnancy also cause increases in ESR. Sickle cell disease, corticosteroids, and heart failure will cause decreases in sed rate. ESR can also be useful in monitoring disease activity in patients diagnosed with rheumatoid arthritis, temporal arteritis, osteomylelitis, polymyalgia rheumatica, and Hodgkin's Disease.

 

Thrombocytes (Platelets)

Platelets (thrombocytes) comprise the smallest and most fragile of all cellular components in the blood. 21 The flattened disc-like cells originate as buds from large megakaryocytes and serve primarily to affect the coagulation process. Unlike other blood cells, the surface of the platelet is riddled with holes, much like a sponge. In circulation, platelets repel other platelets and the endothelial lining of the vascular lumen. Endothelial injury induces a series of biochemical changes in platelet activity ultimately affecting the morphology and beginning the coagulation process. 1 Coagulation is a complex process characterized by various interdependent subprocesses intended to form a hemostatic plug. Also occurring during coagulation is the activation of the actin-myosin contractile system which serves to stimulate contraction of platelets, thereby enhancing the strength of the hemostatic plug. 21,22 Platelets also conduct passive surveillance of blood vessels in search of compromised endothelial lining. 1 Repair of damaged blood vessels is supported by enzymatic systems capable of forming both adenosine triphosphate (ATP) and adenosine diphosphate (ADP), which serve to synthesize prostaglandins, causing increased endothelial swelling and early repair. 23 In addition, platelets are known to produce a growth factor that promotes replacement of damaged cells by stimulating smooth muscle cells and fibroblasts to multiply. 1 Normal platelet counts range from 150,000 to 400,000/mm3 (Table 3). 12,24 Decreased platelet counts (thrombocytopenia) can be attributed to failure of the bone marrow to produce platelets, sequestering platelets by the spleen, increased destruction by antibodies or medications, or a consumptive coagulopathy (as is the case with disseminated intravascular coagulation [DIC]). 12 In addition, various medications may cause thrombocytopenia. See Table 4 for a partial list of medications known to cause thrombocytopenia. Spontaneous bleeding can occur at counts of 50,000 or less. 12 Thrombocytosis is defined as a platelet count that exceeds the high end of normal, and is classified as either primary or secondary. Primary thrombocytosis occurs when megakaryocyte proliferation and maturation bypass normal regulatory mechanisms. 12 Patients with chronic myeloproliferative disorders are at increased risk for developing primary thrombocytosis. Secondary thrombocytosis occurs when the increased platelet count is caused by another disease or condition and resolves when the primary condition is treated. 12

  
Table 3 - Click to enlarge in new window Coagulation Laboratory Values
 
Table 4 - Click to enlarge in new window Medications Known to Cause Thrombocytopenia*

Hemostasis and Coagulation Studies

Normal hemostasis is dependent upon the complex interaction of plasma coagulation and fibrinolytic proteins, platelets, and the blood vasculature. Hemostasis functions to prevent blood loss from disruptive injury to blood vessels and to prevent blood from leaking out of intact vessels. 1 It occurs in two stages: primary and secondary. The primary stage begins immediately after injury and is characterized by vascular constriction, platelet adhesion, and fibrin formation by soluble plasma proteins. In cases where vascular and tissue injury are implicated, vascular constriction results from activation of the sympathetic nervous system and local myogenic activity. 25 In the secondary stage, the soft fibrin clot is stabilized and vasoconstriction is maintained by secretion of serotonin, thromboxane, and prostaglandin. Serotonin serves a both a potent vasodilator and vasoconstrictor but its complete function is not yet known. 26 Thromboxane is the principal metabolite of arachidonic acid in platelets responsible for stimulating platelet activation, and intravascular aggregation of platelets. Like serotonin and thromboxane, prostaglandins have been implicated in diverse physiologic processes. Prostaglandins exert physiologic action where they are synthesized, thus exhibiting autocoid characteristics. 27 In hemostasis, prostaglandins' vasodilatory and vasoconstrictive attributes are of interest.

 

A detailed discussion of thromboxane, serotonin, and prostaglandin is beyond the scope of this article, and readers are advised to review the literature for additional information.

 

Adequate hemostasis is dependent upon a myriad of factors making accurate and timely nursing assessment essential. A variety of tests can be performed to assess the status and function of the varied processes implicated in coagulation.

 

Bleeding Time

Screening for defects in primary hemostasis is accomplished by evaluating the bleeding time. The bleeding time serves as an in vivo measurement of platelet function and can reveal platelet deficiency. The test is affected by several factors including platelet function, platelet factors, and vascular integrity. 1 The test has special significance for patients with a history of familial bleeding or patients undergoing major surgery who may be at risk for hemorrhage. 12 While a variety of techniques are available to assess bleeding time, the most commonly used is the template method whereby a small incision of consistent length and depth is made on the forearm and the amount of time required for the incision to stop bleeding is measured. 12 A modified template method, differentiated only by the length of the incision, is also used. In order to obtain accurate bleeding time results, it is critical that the patient avoid aspirin or aspirin-like products for at least 7 days prior to the test. 1 A platelet count should be assessed prior to testing bleeding time. Platelet counts <100 x 109 /L will increase bleeding time. 1 A prolonged bleeding time in the presence of a normal platelet count indicates platelet dysfunction. 1,12 Conditions associated with prolonged bleeding times include thrombocytopenia, liver disease, von Willebrand disease, uremia, Glanzmann's thrombasthenia, and afibrinogenemia. The normal value for bleeding time is dependent upon the method used for assessment. Normal values for two methods, the template and modified template methods, range from 2 to 8 minutes and 2 to 10 minutes, respectively (Table 3). 12

 

Prothrombin Time

Measurement of prothrombin time (PT) is a common practice in the critical care setting. PT measures the time required for a fibrin clot to form when the extrinsic pathway for coagulation is initiated. PT values are useful in the evaluation of patients with inherited or acquired deficiencies in the extrinsic or common pathway of the coagulation cascade. More commonly, PT is used to monitor therapeutic effectiveness of oral anticoagulation therapy. For patients receiving oral anticoagulation therapy, the goal is typically to maintain the value at 1.5 to 2.5 times the control value, depending on the therapeutic indication. 12 PT values exceeding 2.5 times the control could be indicative of deficiencies in fibrinogen, prothrombin, or factors V, VII, or X. 12

 

Normal values of PT are variable and depend upon the method of testing inclusive of instrumentation and control plasmas. 1 The World Health Organization has adopted a standard thromboplastin reagent and reporting method intended to reduce variability in reporting and to guide long-term oral anticoagulation therapy. The resulting standard reporting method is known as the International Normalized Ratio (INR). It is important for clinicians to understand that the INR is not a laboratory test. Rather, it is a mathematical calculation that corrects for the variability in PT results attributable to the variable sensitivities of the thromboplastin agents used by laboratories. 28

 

The normal range for PT is 11 to 15 seconds (Table 3). 12 Values will be increased in patients with liver disease, factor deficiencies (see above), and in patients using oral anticoagulants. PT values may be decreased in patients with certain forms of cancer, blood clots, and in patients using birth control pills.

 

Because therapeutic INR values are dependent upon the International Sensitivity Index (ISI) of the reagent used in testing, each organization should determine its unique therapeutic INR ranges for various indications. 29 In general, the therapeutic range for patients receiving oral anticoagulants for hypercoagulable states is 2.0 to 3.0, while the therapeutic INR goal for patients with prosthetic heart valves range from 2.0 to 3.5 and depend upon, among other variables, valve position, presence of atrial fibrillation, and whether the valve is bioprosthetic or mechanical. 29,30

 

Partial Thromboplastin/Activated Thromboplastin Time

The intrinsic pathway of the coagulation cascade which is composed of factors XII, XI, IX, VIII, X, V, prothrombin, and fibrinogen, is assessed by either the activated partial thromboplastin time (APTT) or the partial thromboplastin time (PTT). These tests are useful in identifying patients with inherited or acquired deficiencies in the intrinsic pathway or the common pathway of the coagulation cascade. Because congenital coagulation abnormalities, including hemophilia A, hemophilia B, and factor XI deficiency, arise from the intrinsic pathway, the APTT and PTT are commonly used to assess for preoperative bleeding tendencies. 12 The APTT and PTT are also used to monitor therapeutic effectiveness of unfractionated heparin anticoagulant therapy as well as detecting inhibitors of blood coagulation. 1

 

The "activated" in APTT refers to the use of the activator kaolin, which shortens the clotting time of the patient's blood. The APTT is preferred over the PTT because it is more sensitive and more easily reproduced. 12 The normal range for APPT is 25 to 38 seconds and PTT normal values range from 60 to 70 seconds (Table 3). 12 Both APTT and PTT values may be prolonged in patients with liver disease, DIC, and various factor deficiencies. 12 In addition, reductions in any coagulation factor by 25 to 40% will result in prolonged APTT and PTT clotting times. 1 It is interesting to note that while coumadin therapy is associated with prolonged PT values, both APTT and PTT values can be prolonged in the presence of high-dose coumadin therapy. 31

 

As with PT measurements, there is considerable variability in the sensitivity of the different commercially available reagents used to test APPT and PTT. Variability in sensitivity is important in the case of unfractionated heparin, which depends on APPT and PTT testing for assessment of therapeutic effectiveness. Heparin-responsiveness of the in vitro reagents used to determine APTT/PTT can vary significantly. This variation in heparin-responsiveness is observed not only when reagents from different manufacturers are compared, but also when different lots of the same reagent are compared. To ensure accuracy and safety, experimentally establishing a therapeutic range for APTT/PTT results by correlating the observed APTT/PTT with heparin levels is suggested when APTT/PTT reagents are changed. 32 Clinicians should become informed of their institution's practice as it relates to heparin response curve determination. Care delivery driven by the interpretation of lab values requires sound data generated in a scientific manner.

 

Thrombin Time

Thrombin time (TT) measures the conversion of fibrinogen to fibrin. Specifically, it evaluates the common final pathway of the coagulation cascade and provides an estimation of fibrinogen levels. It is also used to monitor fibrinolytic therapy and the presence of heparin-like anticoagulants. 33 A TT >1.3 times the control is indicative of effective anticoagulation with heparin. 12 Thrombin time normal range is 10 to 13 seconds (Table 3). 12 Increased values are representative of low fibrinogen levels, disseminated intravascular coagulopathy (DIC), and liver disease. Thrombin time less than the reference range is not associated with any clinical condition is usually related to improper procedure.

 

Activated Clotting Time

Activated clotting/coagulation time (ACT) is a bedside testing process frequently used to monitor high-dose heparin-induced anticoagulation during cardiac bypass surgery or in the cardiac catheterization laboratory. Other uses for the ACT include monitoring anticoagulation prior to sheath removal and measurement of heparin anticoagulation for patients undergoing extracorporeal membrane oxygenation (ECMO) or hemodialysis therapies.

 

While commonly used, the ACT is not without limitations. It is less precise than APTT and lacks high correlation with both APTT and antifactor Xa levels. 34 In addition, the variability of ACT readings noted during cardiopulmonary bypass therapy has been attributed to the hypothermia and hemodilution that occur. 35 Finally, other variables (including platelet count, platelet function, lupus anticoagulants, and a variety of factor deficiencies) influence ACT data often rendering them questionable.

 

Reference ranges for ACT, like many coagulation studies, are highly variable and dependent upon the method but ranges typically fall between 70 and 180 seconds. Goals for cardiopulmonary bypass are to exceed 400 to 500 seconds, while the goal for patients undergoing percutaneous or surgical revascularization is 300 to 350 seconds during the procedure. 36,37 Sheath removal is recommended when the ACT falls to <150 to 180 seconds. 38

 

Fibrinogen Levels

Several methods exist to quantify fibrinogen (factor I) levels. The established normal fibrinogen level range is 200 to 400 mg/dL (Table 3). Increased levels are associated with the inflammatory response process, menstruation, hyperthyroidism, pregnancy, and acute infection while decreased levels may be attributed to severe liver disease. 12,39 In addition, the consumptive characteristics of DIC are known to deplete fibrinogen levels. Clinicians are reminded that precipitous drops from high-normal values to normal or low-normal values may indicate the development of pathology despite values within the "normal" range.

 

Fibrin Split Products and D-dimer

Fibrin spilt products (FSP), also known as fibrin degradation products (FDP) are distinct protein fragments that result from the asymmetric, progressive breakdown of fibrin clot by plasmin. These fragments (products) are cleared from the circulation by the liver. 1 Four products are formed during the degradation process including X, Y, D, and E. The fibrin fragments, or "fibrin split products," when present in sufficient concentrations, retain some anticoagulant effect through various mechanisms including direct competition with fibrinogen for thrombin, and polymerization of fibrin monomers, thereby interfering with platelet aggregation and, subsequently, the hemostatic platelet plug formation. 12 The normal value for FSP is defined as 2 to 10 [mu]g/mL (Table 3). Conditions including fibrinolysis, DIC, and various obstetrical conditions such as abruptio placentae, preeclampsia, and intrauterine death cause FSP values to increase. 12 Certain conditions, such as deep vein thrombosis (DVT) and pulmonary embolism, may cause an increase in D-dimer, one of the specific degradation products of fibrin. 40-44 Research data suggest that normal D-dimer levels (<400-500 ng/mL) in patients with low pretest probability have <1% probability risk of posttest DVT (Table 3). 40-44 The positive likelihood ratio of positive D-dimer assay results for DVT is approximately 1.8 (specificity approximately 50%); a positive result indicates that further patient testing is required to confirm or exclude the diagnosis of DVT. 41 D-dimer levels may also be elevated in patients diagnosed with sepsis, infections, myocardial infarction, DIC, and surgery within 1 week of test. D-dimer should not be used to assist in the diagnosis of thromboembolic disease for several patient populations including: patients with concurrent anticoagulant use, comorbid cancer, >70 years of age, and patients in an immediate postsurgical state. 45,46

 

Anemia Case Study

Mr M is an active 82-year-old Caucasian male who presented to his primary care physician with a chief complaint of 2 months of progressive dyspnea on exertion. His medical history is significant for coronary artery disease with a myocardial infarction and bypass surgery in 1991, type 2 diabetes mellitus, hypertension, hyperlipidemia, and TURP (transurethral resection of the prostate) in 1980. He prides himself on having been able to "shovel his own snow" until lately. The review of systems reveals that Mr M slept at least 9 hours every night for the last 2 months but he still feels tired when he wakes in the morning. He denies chest pain. He reports no recent changes in his diet or medications. Mr M denied any hematochezia, or melena (though his stools were guiac positive on heparin therapy initiated precatheterization). He had no history of renal failure or insufficiency. He denied alcohol use and had no other medical problems or injuries. Other than some slight urinary hesitation, Mr M reports no other GU (genitourinary) problems. All other systems are normal. His family medical history shows that his father died at age 63 from a heart attack, and his mother died at age 70 from colon cancer. His one living brother, age 77, is in good health. Mr M and his wife of 60 years have one healthy son, age 55, who lives in Colorado.

 

Physical Exam

The following findings were obtained during Mr M's physical exam:

 

* Vital signs: temperature 36.9[degrees]C, heart rate 116 bpm, blood pressure 94/54, respiratory rate 22/min

 

* HEENT (head & neck/ears/eyes/nose/throat): mucous membranes dry and pale

 

* Heart: rapid, regular, no clicks, rubs, or murmurs

 

* Lungs: clear to auscultation A & P (anterior and posterior) bilaterally

 

* Abdomen: soft, nontender, normal bowel sounds, no masses

 

* Extremities: unremarkable

 

* Neuro: cranial nerves II-XII intact, no focal findings

 

 

A complete blood count (CBC) and basic metabolic profile (BMP) were ordered. Tests appear below followed by the result:

 

* Red Blood Cells: 4.22 x 106 mm3

 

* Hemoglobin: 7.9 g/dL

 

* Hematocrit: 28.3%

 

* Mean corpuscular/cell volume (MCV): 67.1 [mu]mm3

 

* Mean cell hemoglobin (MCH): 18.7 g/dL

 

* Mean cell hemoglobin concentration (MCHC): 27.9%

 

* Red cell distribution width (RDW): 16.1%

 

* Platelets: 192,000/mm3

 

* White blood cells: 7.4

 

* Sodium: 140 mmol/L

 

* Potasium: 4.4 mmol/L

 

* Chloride: 98 mmol/L

 

* Carbon dioxide: 28 mmol/L

 

* Blood urea nitrogen: 14 mg/dL

 

* Creatinine: 0.8 mg/dL

 

* Glucose: 104 mg/dL

 

 

Interpretation

Mr M's hemoglobin of 7.9 g/dL reveals a significant anemia. Normal hemoglobin in men is 13-18g/dL. The hemoglobin is the iron containing pigment of the RBC that carries oxygen and is a direct indication of the oxygen transport and delivery. This value can be decreased in hypervolemia; however, Mr M's lungs were clear, he had no JVD, peripheral edema and his chest X-ray was normal. His hematocrit of 28.3% was also well below the normal range for males of 45 to 54%. The hematocrit represents the percentage volume of blood composed of erythrocytes. This value should be three times the value of hemoglobin, and similarly can be affected by dehydration (increased) or hypervolemia (decreased). Mr M's mean cell/corpuscular volume (MCV) of 67.1 [mu]/mm3 is significantly lower than the normal for males of 81 to 98 [mu]/mm3. The low value reflects a microcytic condition and should prompt the nurse to consider the various microcytic anemias, including iron deficiency anemia, in the differential diagnosis. The low MCV indicates that the RBCs individually and collectively, are small, and have low volume of hemoglobin, and thereby contribute to health problems. The patient's low MCH, a reflection of RBC weight, lower than normal MCHC, and wide RDW are also consistent with a diagnosis of iron deficiency anemia. The MCHC reflects overall low mean concentration of hemoglobin in the average RBC, which affects the patient's oxygen-carrying capacity. The wide RDW indicates there is great heterogeneity in the patient's RBCs (there are a variety of RBC sizes). RDW is important in distinguishing thalessemia from iron deficiency anemias. In our case, the wide RDW clearly indicates that iron deficiency anemia should be considered as a contributing factor to his medical condition. Finally, the report of "being tired" after 9 hours of sleep is significant and should be considered in light of Mr M's other clinical issues.

 

Other labs were ordered including serum ferritin, serum iron, and TIBC-all revealing iron deficiency anemia. His physician performed a stress test, which was markedly positive for ischemia, and a cardiac catheterization ensued with sirolimus stent placement for revascularization. Because Mr M was symptom free precatheterization, his heparin therapy was discontinued due to his heme-positive stools. It is very likely that Mr M's anemia contributed significantly to his is-chemic condition and dyspnea. In addition, his elevated heart rate (116 bpm) and a blood pressure of 94/54 mmHg were also signs of insufficient circulating volume for a person with a history of hypertension. Mr M's diabetes may have somewhat masked the chest pain. Later tests including serum iron, TIBC, reticulocytes, transferrin, and ferritin all confirmed iron deficiency anemia.

 

The most likely cause of Mr M's anemia is gastrointestinal blood loss. Mr M requires a workup to rule out colon cancer and any other potential causes of gastrointestinal bleeding.

 

Summary

Hematologic abnormalities are common in patients with critical illnesses. A clear understanding of pathology and the ability to interpret accurately laboratory data are expectations of the APN. It is imperative that information gleaned from assessment of clinical laboratory data be reviewed and considered in concert with the other mechanisms by which nurses acquire patient data. Clinical data in isolation are of little value to the prudent nurse who seeks clinical correlates and subjective patient information in an attempt to create an accurate picture of the patient's state of health. As nurse scientists and others uncover new and deeper understandings of the complex nature of illness, the need to better understand aberrations in health will only increase.

 

New laboratory tests and new mechanisms by which we gather laboratory data are ever present. Understanding contemporary laboratory data and their importance in developing plans for the delivery of care will better position APNs for success in the future.

 

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