Rare Bleeding Disorders

 ASH review series

1. Factor XI def: typically isolated PTT prolongation, manifests as bleeding after surgery, common in certain Jewish population

- also called hemophilia C

-AR or AD inheritance

- weak connection between severity of bleeding and factor 11 levels

Mainstay of factor 11 def treatment: antifibrinolytics, OK to use periop FFP( prior bleeding hx or level < 10%)also can use rFactor 7.

2. Factor VII def: 

-AR inheritance

- correlation between level and bleeding intensity not clear but better than factor 11.

-PT elevation isolated, rest PTT, thrombin time , reptilase time WNL

-Severe bleeding if less than 10%

-4% can present with VTE ( Pearl for boards--> the factor def that can present with thrombosis)

RX- Antifibrinolytics, factor VII a replacement

3. Factor X def: can be acquired or inherited

Both mucocutaneous and visceral bleeding ( including intracranial)

-both PT and PTT prolonged, TT normal

- associated with AL amyloid and myeloma

- Factor X concentrates, FFP

-Level correlation good

4. Factor V def is very rare

- inherited, can be combined with factor 8 def in LMAN or MCFD mutations

-acquired ( bovine thrombin, Quebec plt disorder, autoantibodies to factor V)

-prolonged PT and PTT, level correlation poor

-can treat with platelet transfusion in addition to FFP

5. Factor 13 def: rare

PT and PTT normal

Can present in infancy with umbilical stump bleeding or intracranial bleeding, pregnancy loss, poor wound healing

-Clot lysis test for diagnosis

Imp: 95% time, the def is in factor 13 A subunit. If so, can treat with recombinant factor 13. If in the B subunit ( 5% of cases), use FFP or cryoppt which has both A and B units.

To differentiate between the 2 types, a genetic test is needed.

Level correlation good.

If factor 13 level less than 10%, use monthly prophylactic infusions of recombinant factor 13 ( pearl)

6. Factor 2 def:

Prothrombin def. Can be acquired in APLA.

Typically reptilase time is normal but if APLA is associated with antibodies against factor 2, PT gets prolonged and patient may bleed.

Rx: PCC

Prophylaxis: Weekly prophylaxis if < 10% levels

Poor correlation of clinical manifestations with level

7. Fibrinogen def or factor I: 

quantitative or qualitative

Afibrinogenemia--> neonatal umbilical stump bleeding

Dysfibrinogenemia: can have thrombosis risk

PT, PTT, TT and reptilase time all prolonged

( TT can be prolonged by heparin but reptilase time is prolonged only by problems with fibrinogen)

Rx: Fibrinogen concentrate, FFP, cryo

8. Vit K dependent coagulation factor def--mutation of vit K epoxide reductase or gamma glutamyl carboxylase. Normal vit K level. Treat with vitamin K

9. Alpha 2 antiplasmin def and PAI-1 def: treat with antifibrinolytics

10. Acquired hemophilia: autoimmune or cancer

Mucocutaneous bleeding, RP bleeding, or abd bleeding

Rx: FEIBA, rVIIA, rfactor 8 porcine

Emicizumab not approved, but can be used

Cytoxan + steroid+ rituxan to eradicate antibodies

No role for immune tolerance

11. HHT: AD inheritance

Mutations in TGF b--> excess  angiogenesis

Curacao criteria, Genetic tests for diagnosis

Can be a picture question with Xray of lung with AVM, etc

IV iron, PRBC, antifibrinolytics, Oral thalidomide or IV avastin, local nose procedures, laser etc or other ablative therapies

12. Heyde's ( pronounce Heidi) syndrome:

Aortic stenosis, AVM in bowels, acquired VWD 2 A

Check for VW multimers, acquired type 2 A VWD

Rx: AV replacement, fibrinolytics, octreotide