Anticoagulation, Coagulation mixing studies

Anticoagulation, Coagulation mixing studies

Dosing IV Heparin and PO Coumadin

• Follow nomogram

• Ensure no bleeding (nose, mouth, IV sites, urine, stool, vagina…etc….)

• recheck PTT in 6 hours (for Heparin dose adjustment) or check PT/INR in AM (for Coumadin dose adjustment)

Heparin 1000 cc/hr or 750 cc/hr. Given as 25,000 units in 250 ml D5W. Next PTT in 6 hours after heparin started.

Loading: 60 U/kg bolus F/up with 14 U/kg/hr

Screening Test Abnormalities in Inherited and Acquired Coagulopathies

Mixing study:

• • Useful if ▲ PT or ▲ PTT.

  • Mix Pt's plasma 1:1 with normal plasma and retest. PT/PTT normalizes which means there is a factor deficiency. If PT/PTT remains elevated, it implies that there is a factor inhibitor. Factor VIII antibody is he most common cause. Check for lupus anticoagulant.

  • Coagulation factor levels are useful if mixing study suggest factor deficiency. In DIC all factors are consumed; therefor ▼ factor V and VIII.

  • Vitamin K deficiency → ▼ factors II, VII, IX, X (and protein C, S); therefore normal factor V and VIII.

Lupus anticoag test is assoc with increased risk of thrombosis and recurrent spont. AB. Lupus anticoag is a lab artifact, produces invitro prolonged aPTT. Does not cause bleeding d/o. Seen in 5 - 10% of Pts with SLE and taking Phenothiazines.

Checked as anticardiolipin Abs: IgA, IgG, IgM (<12 APL, <15 GPL, and <12 MPL)

Russel viper venom (RVV) is more sensitive assay for checking lupus anticoag.

Pts with antiphospholipid syndrome have mod. or high levels of cardiolipin abs and are +ve for IgG only or IgG and IgM.

Hemophilias

• Hemophilia A (factor VIII) deficiency

  • X linked

• Hemophilia B (factor IX) deficiency

• Classification

  • mild - 5 to 25% normal factor activity

  • moderate - 1 to 5%

  • severe - <1%

• Clinical manifestations: hematomas, hemarthroses, bruising, bleeding (mucosal, GI, GU)

• Dx: ▲ PTT (normalizes with mixing study), normal PT & vWF; ▼ factor VIII or IX

• Treatment: purified/recombinant factor VIII or IX concentrate, desmopressin (mild disease), aminocaproic acid; recombinant factors VIIa if factor inhib, cryo (only has factor VIII)

Coagulation factor inhibitors

• Etiologies:

  • Hemophilia

    • Tx: replacement of factor VIII in hemophilia A; factor IX in hemophilia B)

  • Postpartum lymphoproliferative disorders and other malignancies

  • Autoimmune diseases, most commonly anti-factor VIII

• Diagnosis: ▲ PTT (does not normalize with mixing study); Bethesda assay quantitates titer

• Treatment: high titer → recombinant factor VIIa, porcine factor concentrates, activated PT complex; others → high-purity human factor, plasmapheresis, immune tolerance.

Vitamin K deficiency

• Etiologies: malnutrition, ▼ absorption (ABx suppression of vitamin K-producing intestinal flora or malabsorption), liver disease (▼ stores), warfarin