A 40YearOld Woman With a Painful and Swollen Calf

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A 40-Year-Old Woman With a Painful and Swollen
Calf

• Based upon LABORATORY MEDICINE CASEBOOK. An
  introduction to clinical reasoning
• Jana Raskova, MDProfessor of Pathology
  Laboratory MedicineUMDNJ-Robert Wood Johnson
  Medical SchoolPiscataway, NJStephen Shea, MD
  Professor of Pathology Laboratory
  MedicineUMDNJ-Robert Wood Johnson Medical
  SchoolPiscataway, NJFrederick Skvara, MD
  Associate Professor of Pathology Laboratory
  MedicineUMDNJ-Robert Wood Johnson Medical
  SchoolPiscataway, NJNagy Mikhail, MDAssistant
  Professor of Pathology Laboratory
  MedicineUMDNJ-Robert Wood Johnson Medical
  SchoolPiscataway, NJ

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Laboratory tests used in coag

• Common aPTT, INR (PT), thrombin clotting time
  TCT, bleeding time, D-dimer
• Other mixing test (whether an abnormality
  corrects if the patient's plasma is mixed with
  normal plasma), antiphosholipid antibodies,
  coagulation factor assays, genetic tests (eg.
  factor V Leiden, prothrombin mutation G20210A),
  dilute Russell's viper venom time (dRVVT),
  platelet function tests, thromboelastography (TEG
  or ROTEM).

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CLINICAL HISTORY AND PRESENTATION

• 40 y.o. female presents with pain and swelling of
  two days duration in the right calf
• Married, mother of 16 y.o. daughter
• Frequent long distance traveler
• No significant past medical or surgical hx.
• No medications with exception of oral
  contraceptives
• Physical exam alert, oriented ?in no acute
  distress
• BP 160/76 mmHg, HR 64 bpm and regular, Temp. -
  99 F, and respiratory rate 18 per minute

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Questions History and Presentation

• What diagnosis is suggested by this history? Why?
• Deep Vein Thrombosis. Why?
• A middle-aged ?, sedentary smoker taking
  contraceptives and confined for long periods of
  time in travel? ? risk for developing a DVT
• The use of contraceptives AND smoking greatly
  increase the risk of DVT
• Significance Most serious complication of DVT is
  pulmonary embolus

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Pertinent Findings

• Edema right calf
• Tenderness in the upper posterior portion of the
  calf
• Positive Homans sign (pain on dorsiflexion of
  the foot)
• Pulses present in both lower extremities
• Patient was admitted to hospital

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What is Homans sign?

• Passive dorsal flexion (bending of the foot
  towards the calf) causes pain in the calf
  muscles.
• The mechanism is thought to involve placing
  traction on the posterior tibial vein ? pain if
  the patient has a deep vein thrombosis
• Indicative of established venous thrombosis
  (inflammation of a vein usually associated with a
  clot) of the leg.
• Accurate in only about ½ the cases. Better
  procedure venography.
• The test has fallen into disfavour because of the
  risk of precipitating a pulmonary embolism.
• http//www.hospitalphysician.com/pdf/hp_mar01_homa
  n.pdf

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Smoking and coagulation

• inflammation
• increased thrombogenesis
• plasma fibrinogen levels are elevated
• further elevated during acute COPD exacerbation
• oral contraceptives cause significant increases
  in fibrinogen levels in smokers and nonsmokers
• only the latter appear to have a compensatory
  increase in antithrombin III activity
• Factor XIII (stabilizes fibrin clots) is
  increased in smokers
• passive smoke is positively correlated with blood
  coagulation activity
• exposure to nicotine may also increase
  plasminogen activator inhibitor-1 (a major
  regulator of fibrinolysis)

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Thrombosis -major complication

• Pulmonary embolism
• 10 have it as a clinical event
• 75 asymptomatic
• 15 in between these
• myocardial infarction
• stroke
• skin ulcers, renal thrombosis,
  gastrointestinal ischemia

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Pulmonary Embolism (PE)

• Sudden cough, which may produce bloody sputum
• Rapid breathing or sudden shortness of breath,
  even at rest
• Chest pain, which may be sharp or stabbing or may
  be burning, aching, or dull chest pain may
  worsen with deep breaths, coughing, eating, or
  bending
• Rapid heart rate
• 911 or ER

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HEMATOLOGY - Admission
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HEMATOLOGY Admission 2

• What does the increased MCV and MCH and the
  decreasesd Hgb suggest? Why?
• Macrocytic anemia

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What is the significance of altered CBC

• ? MCV mean corpuscular volume
• ? RBC
• ? MCH mean corpuscular hemoglobin
• Normal MCHC mean corpuscular hemoglobin
  concentration
• Compatible with macrocytic anemia
• No relationship to deep vein thrombosis, blood
  loss (acute or chronic) or acute inflammation
• Vitamin B12 and folate deficiency are common
  causes of macrocytic anemia.

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Megaloblastic anemia

• Two most common problems ? megaloblastic anemia
• Vitamin B12 (cobalmin) deficiency
• Almost always due to vitamin B12 malabsorption
  (Pernicious anemia)
• Folic acid deficiency
• Many causes
• Dietary Infancy, pregnancy, malnutrition,
  alcohol
• Intestinal malabsorption
• Drug interactions phenytoin, oral contraceptives
• ? demand (preg., infancy, adolescence
• Defective synthesis Liver disease, antifolate
  drugs, ETOHism

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CHEMISTRY - Admission
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Additional Chemistry
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LDH (LD) Lactate Dehydrogenase

• Found in virtually all tissues stable at RT,
  deteriorates with freezing
• Elevated in virtually any disease state in which
  there is cell damage or destruction. POOR
  SPECIFICITY,
• Catalyzes conversion of lactate to pyruvate using
  NAD as a cofactor.
• Five isoenzymes, of total normally present in
  serum, sources
• LDH1 (29-37) - Heart, brain, RBCs
• LDH2 (42-48) - Heart, brain, RBCs
• LDH3 (16-20) Brain, kidney, lung
• LDH4 (2-4) Liver, sk. Musc., kidney
• LDH5 (.5-1.5) Liver, sk. Musc., ileum
• Normal pattern LDH2gtLDH1 plus smaller amts of
  LDH3-LDH5
• Disregard modest elevations
• LDH1gtLDH2 Myocardial infarction
• Erythrocytes have extremely high content of LDH,
  even a small amount of hemolysis will result in a
  ratio falsely suggesting an MI.

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Conditions Affecting LDH activity

• ???? Elevation (gt5 x normal)
• Megaloblastic anemia, widespread carcinomatosis
  (esp. liver), septic shock and hypoxia,
  hepatitis, renal Infarction, and thrombotic
  thrombocytopenia purpura
• ??? Moderate Elevation (3-5 x normal)
• MI, Pulm. Infarction, Leukemias, Inf. Mono.,
  Delerium tremens, Musc. Dystrophy
• ? Slight Elevation (lt 3 x normal)
• Most liver diseases, nephrotic syndrome,
  hypothyroidism, and cholangitis

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Anemia Assessment

• ?Normocytic, normochromic anemia
• Reticulocyte ?
• Hemolytic disease
• Acute blood loss
• Reticulocyte normal
• Malignancy
• Myeloma
• Chronic Disease
• Macrocytosis is seen in
• Megaloblastic anemias ?
• vitamin B12 and folate deficiency
• Some forms of chronic liver disease
• Microcytosis and hypochromia
• Iron deficiency anemia
• Spherocytosis
• Some forms of anemia of chronic disease

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Peripheral Blood Smear
Patient
Normal

• Consistent with macrocytic, hyperchromic anemia
• Red cell population is decreased in number
• Anisocytosis, poikilocytosis with ovalocytes,
  elliptocytes and hypersegmented neurtophils
• N.B. None of this information adds anything to
  the automated hematology count shown earlier

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Deep Vein Thrombosis - Histology

• PatientOver time a thrombus leads to
  inflammatory changes in the wall of the vein.
  Wall is markedly thickened. Clot is partially
  organized and undergoing partial resoluton
• NormalWalls not thickened, lumens patent, no
  inflammation

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COAGULATION STUDIES
Normal coagulation studies. No evidence of a
hypercoagulable state.Baseline for anticoagulant
therapy.
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Coagulation Studies
PT is relatively insensitive to heparin, but it
is useful in detecting problems in the EXTRINSIC
PATHWAY (Factors VII,X,V,II and
fibrinogen). aPTT provies a measure of the
INTRINSIC PATHWAY (prekallikrein, high m.w.
Kininogen, factors XII, XI, IX, VIII, X, V, II
and fibrinogen). MONITORS warfarin therapy).
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Therapy for Deep Vein Thrombosis

• Immediate heparin
• Five days later switch to warfarin.
• Monitor PT, aPTT.

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References

• Erythrocyte Sedimetnation Rate
• http//www.aafp.org/afp/991001ap/1443.html
• Homans sign
• http//www.hospitalphysician.com/pdf/hp_mar01_homa
  n.pdf

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BUN

• Nearly all primary renal diseases increase BUN
• Glomerulonephritis
• Pyelonephritis
• Acute tubular necrosis
• Urinary obstruction

• BUT THERE ARE OTHER IMPORTANT DISEASES THAT ALSO
  INCREASE BUN

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BUN Blood Urea Nitrogen

• Source breakdown of blood, muscle, and protein
• Excreted Entirely by kidney
• Level of BUN is a function of both synthesis and
  excretion

• High
• Renal disease
• Dehydration
• CHF
• GI bleeding
• Starvation
• Shock
• Urinary Tract Obstr.
• Low
• liver disease
• malnutrition

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CREATININE

• Production of Cr depends only on muscle mass,
  rarely fluctuates
• Entirely excreted by kidney
• ONLY renal disorders will affect CR levels

• BUNCr ratio 201
• If BUN gtgtCr think PRE-RENAL dehydration,
  malnutrition, CHF, hepatic failure
• If BUN CR are ?think RENAL

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Review of Labs

• Renal
• BUN 61
• Cr 1.5
• BUNCr 40.7
• Total protein normal
• Albumin ??
• ? Ca related to ? albumin measure ionized
• Hypoalbuminemia with ? pulm. Capil. Hydrostatic
  pressure PULM. EDEMA

• Suggests a non-renal cause for the increase in
  BUN
• Consider
• Dehydration
• CHF/MI
• GI bleed
• Starvation
• Shock
• Urinary tract obstruction