Monday, October 26, 2009

Elevated PT/PTT

Elevated PT
  • Liver disease, cirrhosis
  • Drugs (ie. warfarin*)
  • Defect or decrease in Factor VII
  • Early vitamin K deficiency (inadequate dietary intake, malabsorption, antibiotics altering gut flora)
Elevated PTT
  • Defect or decrease in Factors VIII, IX, or XI
  • Drugs (ie. heparin*)
  • Lupus anticoagulant
  • Hemophilias
  • von Willebrand's disease
Elevated PT and PTT
  • Disseminated intravascular coagulation
  • Late vitamin K deficiency
  • Factor II, V, X deficiency (common pathway)
  • Use of direct thrombin inhibitor (eg. Argatroban, Lepirudin)

Causes of thrombocytopenia

Decreased platelet production
  • Aplastic anemia
  • Bone marrow damage from chemo/radiation therapy
  • Congenital or acquired bone marrow aplasia or hypoplasia
  • Acquired pure megakaryotic aplasia
  • Leukemia
  • Myelofibrosis
  • Myelodysplastic syndrome
  • Damage to megakaryocytes (HIV)
  • Vitamin B12 and folate deficiency
  • Thrombocytopenia with absent radius syndrome
Increased platelet destruction
  • Immune-mediated -- PRIMARY: ITP SECONDARY: infection (HIV, herpes, HCV), SLE, antiphospholipid syndrome, alloimmune destruction (post-transfusion), drugs (heparin-induced thrombocytopenia*, abciximab, quinidine, sufonamides, vancomycin)
  • Non-immune-mediated--- DIC, TTP, HUS, HELLP syndrome, preeclampsia, cardiopulmonary bypass
Sequestration
  • Congestive splenomegaly 2/2 cirrhosis and portal hypertension
Pseudothrombocytopenia (EDTA-induced platelet clumping)
Dilutional thrombocytopenia (after massive PRBC transfusion)

Wednesday, October 21, 2009

Management of Supratherapeutic INR

INR 2.0-3.0
- Therapeutic range

INR 3.0-5.0 without signs of bleeding:
- Lower warfarin dose if INR is minimally supratherapeutic
- Hold warfarin until INR is therapeutic, then resume at a lower dose

INR 5.0-9.0 without signs of bleeding:
- Hold warfarin and monitor INR frequently until INR is therapeutic, then resume at a lower dose
- Hold warfarin and give 1-2.5mg oral Vitamin K1

INR > 9.0 without signs of bleeding:
- Hold warfarin, give 5 to 10mg oral Vitamin K1, and monitor INR frequently until INR is therapeutic, then resume at a lower dose

Any INR with serious or life-threatening bleeding:
- Hold warfarin, give 10mg Vitamin K1 by slow IV infusion, supplement with prothrombin complex concentrate, FFP, or recombinant human factor VIIa, depending on clinical urgency
- Repeat as needed

Tuesday, October 20, 2009

"a" wave in venous pulse

- "a" wave is normally produced by right atrial contraction

Large (Cannon) "a" waves:
- Occurs when atria and ventricles contract simultaneously, causing blood to be pushed up against the AV valve and up the venous system
- Cannon "a" waves occur regularly in junctional rhythm
- Cannon "a" waves occur irregularly in AV dissociation accompanying PVCs, VTach, and complete heart block

Other "a" wave morphology:
- "a" wave absent in atrial fibrillation
- flutter "a" waves in atrial flutter
- variable "a" waves in multifocal atrial tachycardia
- very large "a" waves can occur in pulmonary HTN

Heart Block

1st Degree:
- PR interval prolonged > 200msec
- QRS follows every P wave
- Delay usually in the AV node
- Benign, does not require treatment

2nd Degree Mobitz I:
- Progressive prolongation of PR interval until a P wave fails to conduct
- Block usually in the AV node
- Benign, does not require treatment

2nd Degree Mobitz II:
- P wave randomly fails to conduct, resulting in sudden drops of QRS complexes (no preceding PR interval prolongation)
- Block is in the His-Purkinje system
- Often progresses to 3rd degree heart block, requires pacemaker implantation

3rd Degree:
- AV dissociation: absence of conduction of atrial impulses to ventricles (P waves do not correspond to QRS complexes)
- Separate atrial rate and ventricular rate (ventricular escape rhythm ~25-40bpm)
- Requires pacemaker implantation

Monday, October 19, 2009

Workup of polycythemia

Diagnostic criteria for polycythemia vera (3 major criteria or 2 major + 2 minor)

Major criteria:
- Elevated RBC mass (men > 36 L/kg, women > 32 L/kg; or Hct > 60% in men, > 56% in women)
- SpO2 > 92%
- palpable splenomegaly
Minor criteria:
- Platelets > 400
- WBC > 12
- High leukocyte alk phos > 100
- High B12 > 900
Other findings:
- Low epoetin level (70% sensitivity, 90% specificity for PV)
- Hyperuricemia is common
- Bone marrow biopsy confirms diagnosis

Tests to order in the workup of polycythemia:
- CBC, SpO2, ABG, epoetin level, B12, alk phos

Urinalysis findings in chronic kidney disease

- There are no specific casts that suggest chronic kidney disease.
- Patients with chronic kidney disease may have broad casts in their urine, which derive from damaged and dilated tubules.
- In general, patients with end-stage kidney disease of any cause have very scant urine sediments because there are very few remaining nephrons left that produce dilute urine

Hypercoagulability Workup

Activated Protein C resistance
Factor V Leiden
Prothrombin Gene 20210A mutation
Protein C level, Protein S level (may be low in patients taking warfarin)
Antithrombin III level (may be low in patients taking heparin)
Homocysteine level
Anti-cardiolipin Ab, dilute Russel viper venom time (DRVVT) (high with lupus anticoagulant)
PT/PTT
Factor VIII
Thrombin time

Sunday, October 18, 2009

Saturday, October 17, 2009

Blood Products

- Whole Blood (rarely used, may consider when there is massive bleeding and use of >5-7 units of packed RBCs)

- Packed RBCs (1 unit increases Hct by 3)

- CMV-Negative RBCs (and other blood products)

o Indicated for premature infants and infants less than 4 weeks of age, and immune compromised patients who are CMV seronegative

- Leukoreduced RBCs (and other blood products)

o Removes leukocytes, leukocyte debris, and leukocyte-generated cytokines

o Indicated for transplant patients, patients with previous febrile nonhemolytic transfusion reactions, and CMV seronegative at-risk patients for whom seronegative components are not available

- Irradiated RBCs (and other blood products)

o Indicated to avoid GVHD in immune compromised, transplant, and leukemia patients

- Washed RBCs

o Prevents complications associated with infusion of proteins present in small amount of residual plasma in RBC concentrates

o Indicated for patients with severe or recurrent allergic reactions associated with RBC transfusion, patients with IgA deficiency, and patients with complement mediated immune hemolysis

- Platelets (6 units increase platelets by 30,000/uL)

o Indicated for patients with bleeding due to either thrombocytopenia and/or platelet dysfunction (DIC, TTP, ITP, hypersplenism, AIDS, sepsis, aplasia)

o Whole Blood Platelets: each unit is pooled from 4-6 donors of the same blood type

o Apheresis Platelets: obtained from one donor with use of an apheresis machine

- Granulocytes (neutrophils)

o Always irradiated to prevent GVHD

o Indicated for patients with severe neutropenia and life-threatening bacterial or fungal infection not responsive to antibiotic therapy (ie Candida tropicalis fungemia, vancomycin-resistant Enterococcus faecalis, multidrug-resistant Pseudomonas aeruginosa, and invasive aspergillosis); also indicated for neonates with clinical sepsis and patients with chronic granulomatous disease

- Fresh Frozen Plasma (1 unit increases fibrinogen by 7-10mg/dL)

o Contains all clotting products but no platelets

o Indicated for multiple coagulation factor deficiencies (eg DIC, TTP/HUS, liver disease, warfarin overdose, vitamin K deficiency)

- Cryoprecipitate (10 bags increases fibrinogen by 70mg/dL)

o Contains fibrinogen, VWF, factors V, VIII, XIII

o Indicated for bleeding in VWD, factor XIII deficiency, or factor VIII deficiency

§ Recombinant factor VIII now available for factor VIII deficiency

§ Can be used to prepare fibrin glue

- Cryo-poor Plasma (FFP minus cryoprecipitate)

o Indicated for plasma replacement in TTP and HUS, can also be used in treatment of warfarin overdose and vitamin K deficiency

Causes of Low Anion Gap (AG < 7)

- Laboratory error (most common cause)

- Severe hypernatremia (Na > 170)

- Overestimation of plasma chloride

o Severe hyperlipidemia

o Bromide intoxication (eg pyrodistigmine bromide for myasthenia gravis)

- Decrease in unmeasured anions

o Hypoalbuminemia (AG falls by 2.5 mEq/L per 1g/dL reduction in albumin)

- Increase in unmeasured cations

o Hyperkalemia

o Hypercalcemia

o Hypermagnesemia

o Lithium intoxication

o Multiple myeloma

o Polyclonal IgG gammopathy

Monday, August 10, 2009

Acute vs. Chronic Renal Failure

Acute renal failure (ARF): caused by dehydration, blood loss from major surgery or injury, or the use of medications, such as contrast agents used in X-ray tests, antibiotics such as gentamicin, or nonsteroidal anti-inflammatory drugs (NSAIDS) such as aspirin or ibuprofen.
Chronic kidney disease (CKD): caused by a long-term disease, such as high blood pressure or diabetes, that slowly damages the kidneys and reduces their function over time.

ARF usually presents with decrease urine output and electrolyte abnormalities and sudden elevation of BUN and Cr (BUN more)

CRF usually presents with mild elevation of Cr over a long time and sx's don't present until only 10%-20% kidney function is left. On U/S CRF shows more atrophic kidney

Correcting anion gap for albumin

observed anion gap =
= ((sodium in mEq/L) + (potassium in mEq/L)) - ((chloride in mEq/L) + (HCO3 in mEq/L))
corrected anion gap =
= (observed anion gap) + (0.25 * ((normal serum albumin in g/L) - (observed albumin in g/L)) =
= (observed anion gap) + (0.25 * (44 - (observed albumin in g/L))

Abnormal LFTs

Hepatocellular injury: increase in ALT and AST (AST more in alcoholic liver disease, ALT more in viral hepatitis), (+/-) ALP and Tbili
Cholestasis: increase in ALP and Tbili, (+/-) ALT and AST
Isolated hyperbilirubinemia: increase in Tbili, normal transaminases and ALP

Liver Disease

Acute: First presentation is transaminitis (AST, ALT), ALP (if any obstruction presents)
Chronic: ALT and AST elevated for more than 6 months-> increase bilirubin-> decrease in albumin-> decrease in platelet count-> coagulation factors

Isolated Hyperbilirubinemia

1) Unconjugated:
a) Over production: hemolytic anemia
b) Defective conjugation: Gilbert's syndrome (jaundice when hungry), Crigler-Najjar
2) Conjugated
Defective excretion: Dubin-Johnson, Rotor's syndrome (black liver)

Friday, August 7, 2009

Acute vs. Chronic Renal Failure

DDx for Muscle Weakness

1) Muscle:
a) Congenital myopathies and mitochondrial myopathies: Sx. bilateral, proximal to distal wasting. Dx: elevated CK and LDH, abnormal EMG, normal nerve conduction. definite diagnosis with genetic testing.
b) Polymyositis: Abnormal CK and LDH, Dx with muscle biopsy
c) Dermatomyositis: Abnormal CK and LDH, Dx made with muscle biopsy
d) CREST syndrome: Anti-centromere ab
2) NMJ
a) Myesthenia gravis: Dx with EMG. Contractile force reduced with repetition
b) Lambart-Eaton: Dx with EMG. Contractile force increased with repetition
3) PNS
a) Diabetic Neuropathy: loss of sensation first. abnormal NC labs
b) Peripheral nerve degeneration/demyelination. Abnormal NC studies. Weakness in isolated motor neauron units
c) Radiculopathy: weaknes in motor neuron unit bundles. Abnormal NC studies
4) CNS
a) Gullian-Barre: ascending progression. increased ab levels in CSF
b) MS: lesions on CNS on MRI
c) B12 deficiency: depleted B12 levels
d) Polio
e) ALS: intact sensation, both upper neuron and lower neuron signs

Meld's Score


Thursday, August 6, 2009

Fever of unknown origin

Petersdorf and Beeson criteria:
1) Fever higher than 38.3°C (101°F) on several occasions
2) Persisting without diagnosis for at least 3 weeks
3) At least 1 week's investigation in hospital

Work up:
1) comprehensive histpry with repeated PE
2) laboratory tests: serological, blood culture, immunological
3) studies: U/S to r/o cholelithiasis, echo to r/o endocarditis, CT-scan to r/o infection, abscess, malilgnency. Gallium-67 scanning which seems to visualize chronic infections more effectively.
4) invasive techniques : biopsy and laparotomy for pathological and bacteriological examination
5) PET scan: has been reported to have sensitivity of 84% and a specificity of 86% for localizing the source of fever of unknown origin.
6) systematic discontinuation of medications to r/o drug fever

CHADS2 criteria

Calculating CHADS score:
C : Congestive heart failure, 1
H: Hypertension (or treated hypertension), 1
A: Age more than 75 years, 1
D: Diabetes, 1
S2: Prior Stroke or TIA, 2
Recommendations for anticoagulation:
0: Low risk: daily ASA 81-325 mg
1: Moderate risk: ASA daily or raise INR to 2-3
2 or higher: Moderate to high risk: Warfarin with targer INR 2-3

Tumor lysis syndrome

Cairo-Bishop Definition
1) Laboratory tumor lysis syndrome: abnormalitiy in two or more of the following and occurs within 3 days before or 7 days after chemotherapy.
a) uric acid > 8 mg/dL or 25% increase
b) potassium > 6 meq/L or 25% increase
c) phosphate > 4.5 mg/dL or 25% increase
d) calcium < 7 mg/dL or 25% decrease
2) Clinical tumor lysis syndrome: laboratory tumor lysis syndrome plus one or more of the following:
a) increase serum creatinine (1.5 times upper limit of normal)
b) cardiac arrhythmia or sudden death
c) seizure
(A grading scale (0-5) is used depending on the presence of lab TLS, serum creatinine, arrhythmias, or seizures.)

UA findings in ARF

1) Prerenal: benign sediments or few hyaline casts, (-) protein, (-) blood
2) Intrarenal:
a) ATN: "muddy brown" casts, granular casts, trace protein, (-) blood
b) Acute glomerulonephritis: RBC casts, WBC casts, fatty casts, 3+-4+ protein, 3+ blood
c) Acute interestitial nephritis: WBC casts, eosinophils, 1+ protein, 2+ blood
3) Postrenal: No sediments, (-) protein, (-) blood

Renal Tubular Necrosis

Type I: distal; inability to secrete H+; hpokalemia; Rx: correct acidosis with sodium bicarbonate
Type II: proximal; inability to reabsorb bicarbonate; hypokalemia; Rx: Na restriction
Type IV: distal; hypoaldosteronism or aldosterone resistance; hyperkalemia, H+ in urine

ATN vs. AIN

ATN: Acute tubular necrosis leads to ARF. Causes: 1) ischemic: globar ischemia, shock, hemorrhage, sepsis, DIC 2) nephrotoxic: aminoglycosides, radiocontrast, NSAIDs (especially in the setting of CHF), poisons, myoglobinuria, hemoglubinuria, cisplastin, multiple myeloma (kappa and gamma light chains). Dx: elevation of BUN and Cr and decrease in UOP consistant with ARF

AIN: Acute interestitial nephritis inflammation of the glomerular and tubular interestitium. 10% risk of ARF. Causes: acute allergic reaction to medications (e.g. penicillins, NSAIDs, anticoagulants, thiazides, furosemide, phenytoin, sulfa drugs), infection (streptococcus and legionella pneumophilia), CVD (e.g. sarcoidosis). Dx: increased BUN, Cr, eosinophiluria

ESR

Elevated ESR: severe infection, multiple myeloma, Waldenstrom macroglobulinemia, temporal arthritis, polymyalgia rheumatica

Depressed ESR: polycythemia, extreme leukocytosis, sickle cell anemia

Pseudogout

Risk factors: age, osteoarthiritis, hemochromatosis, hyperparathyroidism, hypothyroidism, Bartter's syndrome

Gout Meds

CHRONIC GOUT:
Xanthine oxidase inhibitors (decrease production): allopurinol, oxypurinol, tisopurine, febuxostat, and inositols

Uricosurics (increase secretion): probenecid, benzbromarone and sulfinpyrazone, EDTA

Urate oxidase (breaks down uric acid deposits): pegloticase
ACUTE GOUT:
NSAIDs (antiinflammatory):diclofenac, etoricoxib, indomethacin, ketoprofen, naproxen
Corticosteroids (antiinflammatory): prednisone
Cholchicine (inhibits neutrophils and uric acid deposition)

Acid Base Problems:

pH=bicarb/PCO2
Metabolic Acidosis: Low bicarb, Low pCO2 (compensation)
Metabolic Alkalosis: High bicarb, High pCO2 (compensation)
Respiratory Acidosis: High pCO2, High bicarb (compensation)
Respiratory Alkalosis: Low pCO2, Low bicarb

Wednesday, August 5, 2009

Cancers with Bone Metastasis:

BLT w/ Kosher Pickle, Mustard, Myo: Breast, Lung, Thyroid, Kidney (renal), Prostate, Multiple Myeloma

Causes of Hyponatremia

Urine Na >10: Diuretics, ACEI, Renal Salt Wasting, Cerebral Salt Wasting, Addison's
Urine Na <10:>Dehydration, Vomiting, Sweating, Diarrhea


Thursday, July 16, 2009

Treating Hyperkalemia

1. Get EKG
2. Ca gluconate- stabilizes cardiac membrane to prevent arrythmias, no effect on K level
3. Albuterol (Beta 2 agonist)- drives K into cell
4. Insulin - drives K into cell: Don't forget to give with Glucose
5. Diuretics- Lasix
6. Kayexalate- GI excretion of K
7. Bicarb- Correct metabolic acidosis
8. Emergent Dialysis

Narcotic Equivalents

Expected Respiratory Compensation In Metabolic Acidosis

WINTER'S FORMULA:
Expected pCO2 = 1.5 *(measured HCO3) + 8 (+/-) 2

Wednesday, July 15, 2009

Indications for Emergent Dialysis

Acidosis
Electrolytes (K)
Intoxication
Overload
Uremia

Correction of Ca in low Albumin

Corrected Ca= (4-albumin)*0.8+(measured Ca)

Hyponatremia in Cirrhosis

it's dilutional and hormonal (ADH)