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)

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

"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

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

Serum Creatinine vs GFR

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