ACD – 8-7-14Yogita Rochlani

History

Elderly person could present with a hematuria and incidentally found to have lots of bruising. Then the following labs:

Labs: What’s the diagnosis?

0Factor V, VII, VIII, I X, X, II <1%0VW factor - WNL0Reptilase WNL0Risotcetin assay WNL0PS: dimorphic microcytic RBC, no schistocytes0Mixing study abnormal

Acquired Hemophilia

Diagnosis

Bleeding HistoryBleeding Disorder

Bleeding Symptoms Platelet defects (primary hemostasis)

Clotting Factor Deficiencies (secondary hemostasis)

Overview of bleeding events

Mucocutaneous (oral cavity, nasal cavity, GI, GU)

Deep tissue (joints and muscles)

Excessive bleeding after minor cuts

Yes Not usually

Petechiae Common Uncommon

Ecchymoses Usually small and superficial

Large subcutaneous and soft tissue hematomas

Hemarthroses Uncommon Spontaneous in severe deficiencies or with trauma in moderate deficiencies

Bleeding with invasive procedures including surgery

Often immediate with degree of bleeding dependent on severity of defect

Procedural or delayed bleeding with degree of bleeding depending on type and severity of defect

Physical Exam

Petechiae (< 3mm) Purpura (> 3mm)

Physical Exam

Ecchymosis

Telangectasia

Physical Exam

Cushing - striaeSenile Purpura

Basic Screening Laboratory Tests CBC

Peripheral Smear

PT/INR- Extrinsic pathway; deficiency of vitamin K, warfarin therapy, liver disease

PTT - intrinsic pathway; to monitor anticoagulation (heparin, parenteral direct thrombin inhibitors) and screen for hemophilia

Thrombin time and fibrinogen level - defects in the common pathway (factor X, V, prothrombin, and fibrinogen.

PT PTT Inherited Acquired

High Normal Factor VII deficiency Vitamin K deficiency (mild) Liver disease (early) Warfarin

Normal High Hemophilia A or B vWD (if F VIII <40%)Contact factor deficiency (XII, HMWK, prekallikrein)

Inhibitor-Non specific (lupus anticoagulant)-Specific (i.e., factor VIII inhibitor)

High High Factor X, V, or Prothrombin deficiencyDysfibrinogenemia/Hypofibrinogenemia

DICVitamin K deficiency (severe) Liver disease (late) Warfarin (supratherapeutic)Inhibitor (Factor V, thrombin)

Normal Normal Factor XIII deficiency Factor XIII inhibitor

DD of prlonged PTT

1. Deficiency

2. Inhibitors

3. APLS

4. Anticoagulant use

Acquired inhibitors of the coagulation system

0Antibodies that decrease activity or increase clearance of clotting factors.

0Antibodies to multiple clotting factors ( II, VIII, IX, XI, XII,XIII) – SLE

0Most common clotting factor affected is Factor VIII.

Predisposing conditions

0Post partum state

0RA, SLE

0Malignancies ( CLL, adenocarcinoma lung)

0Drug induced ( penicillin, sulfonamides, phenytoin, interferons)

Clinical Features

0Large hematomas 0Extensive ecchymoses0Severe mucosal bleeding - epistaxis, gastrointestinal

bleeding, and gross hematuria. (Spontaneous hemarthroses, common in hereditary factor VIII deficiency, are unusual in those with acquired disease. )

Diagnosis

0Exclude the use of heparin – Redraw, correct with Protamine, thrombin time and a reptilase time.

0 Inhibitor screen (mixing test) — initial diagnostic test for a factor VIII. Correction of the prolonged aPTT suggests a factor deficiency or VWD, while persistent prolongation of the aPTT indicates the presence of an inhibitor.

0Addition of phospholipid to serum0For inhibitor specificity – Bethesda assay - establishes the

diagnosis of a factor VIII inhibitor and quantifies the antibody titer.

Treatment0 Non life-threatening bleeding and low inhibitor titers - DDAVP at a dose of

0.3 mcg/kg SQ per day given for three to five days.

0 Low titer inhibitors (ie, <5 Bethesda units) - human factor VIII concentrates at high doses

0 Higher titer factor VIII inhibitors or severe bleeding - activated prothrombin complex (eg, factor VIII inhibitor bypassing activity [FEIBA]) or human recombinant human factor VIIa (rfVIIa).

(eg, typical FEIBA dose 75 units/kg; rfVIIa median starting dose 90.4 mcg/kg, range 45 to 181 mcg/kg).

0 Immunosuppressive therapy - Prednisone, Cyclophosphamide, Rituximab