Physiology-Treatment of Coagulation Disorders

Question 1

Platelet type bleeding

Answer 1

From mucous membranes (nose bleeds, blood in urine, external cuts)

Question 2

Factor type bleeding

Answer 2

Deeper joint bleeds and muscle bleeds

Question 3

What type of bleeding do people with vWF deficiency presents with?

Answer 3

Platelet-type. This is because vWF is necessary for platelet aggregation and adherence to endothelium.

Question 4

Why is PTT extended if a patient has vWF deficiency?

Answer 4

vWF complexes with factor VIII. When vWF is deficient, so is factor VIII which is in the intrinsic pathway.

Question 5

What happens in primary hemostasis?

Answer 5

Vessel injury -> platelet adhesion -> platelet activation -> platelet aggregation -> platelet plug

Question 6

What happens in secondary hemostasis?

Answer 6

Activation of coagulation cascade and formation of fibrin clot.

Question 7

Deficiency in what factors of the coagulation cascade will not cause a bleeding deficiency?

Answer 7

Kallikrein, prekallikrein and factor XII. Note that factor XII will have an elevated PTT, but does not present with a bleeding disorder.

Question 8

A patient presents with spontaneous deep tissue bleeds. He has several brothers, uncles and cousins with the same condition. What are the most common bleeding disorders?

Answer 8

Hemophilia A (VIII) and B (IX). Both are X-linked recessive.

Question 9

What is a specific test for DIC?

Answer 9

D-dimer (indicates that fibrinogen has been activated by thrombin because you can’t get split products until after the fibrin network has formed)

Question 10

A patient presents with a stump umbilical cord and poorly healing wounds. PT and PTT are normal. What clotting factor could be deficient?

Answer 10

Factor XIII. It is responsible for crosslinking of fibrin molecules to form the clot.

Question 11

What are the acquired factor deficiencies?

Answer 11

Vit K (II, VII, IX, X, C & S are present, but not activated), liver failure (not producing factors, except VIII) and DIC (all factors are being used up)

Question 12

How do you treat someone who is bleeding and can’t stop bleeding due to vitamin K deficiency?

Answer 12

Give subQ vitamin K and fresh frozen plasma because it takes time for vitamin K to actually activate the clotting factors.

Question 13

A patient is brought into the ED after a motorcycle accident. He is bleeding and has a history of bleeding easily, but is unconscious. How do you treat him? What risks does this treatment carry?

Answer 13

Fresh frozen plasma is used when the bleeding disorder diagnosis is unknown, multiple factors are needed or the concentrated factor product is not available. He is at risk for volume overload, infection and allergic reactions.

Question 14

What are the main infectious complications associated with transfusions?

Answer 14

Bacteria, viral (hepatitis, HIV, parvovirus) and prion diseases (CJD)

Question 15

What happens when FFP is thawed out at 4 degrees C in the refrigerator? Why is this useful?

Answer 15

You get cryoprecipitate: plasma fraction concentrated for fibrinogen, VIII, XIII and vWF. Although it still carries risk for allergic reactions and infection, it is less volume than FFP and risk for volume overload is decreased.

Question 16

Why does PT become prolonged 1st in liver disease?

Answer 16

Factor VII has the shortest half life. Factor XIII has the longest.

Question 17

How do you need to dose factor replacement therapy?

Answer 17

Frequency (because different factors have different half lives) and amount (because some don’t require as much to become hemostatic)

Question 18

What determines the severity of hemophilia A and B?

Answer 18

5% = mild. And then carriers are mostly asymptomatic.

Question 19

What type of plasma do you use to treat hemophilia A?

Answer 19

Monoclate P. Plasma derived factor concentrate (filtered by affinity chromatography for factors) from a large pool of screened donors. The concentrate is the virally inactivated.

Question 20

How do you treat hemophilia A and B?

Answer 20

Give recombinant factor VIII or IX. 1 unit/kg raises activity level 2% with a half life of 8-12 hours. It is given by slow IV infusion. For mild bleeds (non-life threatening hematoma), you raise activity to 40%. For severe bleeds (deep muscle or retroperitoneal), you raise activity to 100%.

Question 21

A patient with hemophilia A comes in bleeding. You want to get his factor VIII level up to 30%. How many units should you give if he weighs 50 kg?

Answer 21

Dose of FVIII = Wt x Desired % increase x 0.5. 50 x 30 x 0.5 = 750. But you’d actually give the entire vile so you don’t waste factor.

Question 22

Why might recombinate be preferable to monoclate P in treatment of hemophilia A?

Answer 22

Recombinate is a genetically engineered recombinate factor VIII and decreases risk for infection or prion disease. Monoclate P is a plasma derived factor concentrate.

Question 23

Why might advate be preferable to recombinate in treatment of hemophilia A?

Answer 23

Advate is the second generation recombinate lacking the B domain, which means that you don’t need albumin to stabilize it at all. The makes the risk for infection or prion disease 0.

Question 24

What is the new drug that helps prolong the action of replacement factor VIII?

Answer 24

It is complexed with IgG, which lasts longer in the blood stream.

Question 25

What was the old way to treat hemophilia B? Why was it stopped? What is it used for now?

Answer 25

Plasma-derived factor IX. This carried significant thrombotic risk because it also contained factors II, VII, IX and X. It is now used for hemophilia B patients who develop antibodies against factor VIII. This allows them to bypass factor VIII in the clotting cascade with the other factors present.

Question 26

What are AlphaNine and mononine? How do you dose them?

Answer 26

Monoclonal antibody purified native protein and virally inactivated factor IX concentrate. 1 unit/kg raises activity by 1% for a whole day.

Question 27

What is BeneFix and how do you use it?

Answer 27

Recombinant factor IX. Adults get 1.2 units/kg to raise activity by 1%. Kids get 1.4 units/kg to raise activity by 1%. t1/2 is about 16-17 hours.

Question 28

A 30 year old man comes to the ED bleeding. He has a history of hemophilia B. He weighs 70kg and you want to get his factor IX activity up to 80%. How many units of recombinant factor should you give?

Answer 28

70kg x 80% x 1.2 = 6720 units, but you’d finish the last vial completely.

Question 29

A patient with mild hemophilia A is going to the dentist. He does fine without factor replacement. What might you give him to prophylax for the appt?

Answer 29

DDAVP (Stimate intranasal spray or IV/SQ) releases factor VIII and vWF from endothelial stores and is used 30-60 min before procedure. Amicar and tranexamic acid are antifibrinolytics that inhibit plasminogen and keep the clots from going away once they’re formed.

Question 30

What are complications of DDAVP in kids?

Answer 30

Seizures. DDAVP is vasopressin and causes fluid retention -> hyponatremia.

Question 31

When should you not use Amicar?

Answer 31

Antifibrinolytic therapy should not be used with renal/bladder bleeding or joint bleeds.

Question 32

Why would women use DDAVP?

Answer 32

If they have vWF deficiency and experience menorrhagia, they can take this once a month to prevent excess menstrual bleeding.

Question 33

What recombinant factor concentrate is useful for hemophilia A/B with inhibitors, acquired hemophilia, factor VII deficiency or bleeding during surgery/trauma?

Answer 33

Novoseven, recombinant factor VIIa concentrate. It cause direct activation of extrinsic pathway and a direct thrombin burst.

Question 34

When would you use fibrogammin P?

Answer 34

Factor XIII deficiency. It is a human plasma-derived factor XIII concentrate.

Question 35

A 17 year old male comes to the ED after cutting himself at work. He can’t stop the bleeding. His family has a history of similar episodes. You give him recombinant factor VIII to stop the bleeding, but it continues. What do you do now?

Answer 35

You give humate P. This is a plasma-derived product containing factor VIII AND vWF. vWF is AD inherited and is the most common bleeding disorder and is most likely what this kid has. You could also give Stimate (DDAVP), Novoseven (aFVII) or Amicar (antifibrinolytics)

Question 36

When can’t you use DDAVP?

Answer 36

Type II vWF deficiency. This will result in worsened thrombocytopenia.