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Interactive cases

Q: What is the current regular treatment of DVT and PE?

Subcutaneous LMWH follwed by vitamin K antagonists direct oral anticoagulatns with or without initial LMWH

Q: How is unfractionated heparin dosed?

Dosage based on body weight and adjusted by aPTT monitoring

Q: How is LMWH dosed?

Dosage based on body weight and adjusted for renal functino

Q: What are vitamin K antagonists? And how are they dosed?

acenocoumarol, fenprocoumon warfarin Variable dosage based on INR monitoring

Q: How can the effect of vitamin K antagonist be antagonisezd?

vitamin K infusion of prothrombin conentration infusion of plasma

34 important questions on Interactive cases

What are symtpoms of deep vein thrombosis?

red skin
warm
painful calf
swelling
shining skin
pain while walkign

In which percentage of cases with suspected deep venous thrombosis is the clinical diagnosis correct

40%

Which imaging technique is primarily used for the diagnosis of DVT?

ultrasound

What is post thrombotic syndrome?

persistent swollen, painful leg after DVT

Swollen leg
Feel heavy
Pain
varicose veins
discoloration
ulceration

postthrombic pigmentation

What is the current treatment to prevent PTS?

compression stockings

What are symptoms of pulmonary embolism?

breathlessness
pleural pain
hemoptysis
fever
shock

CT scan

What role can a chest-X-ray play in PE?

In acute phase of PE chest x-ray normal
can rule out other diseases mimicking pulmonary embolism
After few days pulmonary infiltrates may be visible

What are diagnostic strategies for PE?

You have a score system
If you have 4 points or less a D dimer test
< 500 ng/ml geen PE

More than 4 ponits:
- CT scan or perfusion scsn

What is the current regular treatment of DVT and PE?

Subcutaneous LMWH follwed by vitamin K antagonists
direct oral anticoagulatns with or without initial LMWH

How is unfractionated heparin dosed?

Dosage based on body weight and adjusted by aPTT monitoring

How is LMWH dosed?

Dosage based on body weight and adjusted for renal functino

What are vitamin K antagonists? And how are they dosed?

acenocoumarol, fenprocoumon
warfarin

Variable dosage based on INR monitoring

How can the effect of vitamin K antagonist be antagonisezd?

vitamin K
infusion of prothrombin conentration
infusion of plasma

How does antagonizing VKA work?

Vitamin K:
first effect after 6 hours
clear effect after 12-24 hours

More vitamin K does not act faster, but will lead eventually to more and prolonged neutralizing of the VKA effect
Intravenous vitamin K does not act substantially faster

Prothrombin complex concetnrate
- contains plasma dervied purifeid vitamin K dependent clotting factors II, VII, IX, x

What are direct oral anticoagulants?

Thrombin inhibitor: dabigatran

Factor Xa-inhibitors:
- rivaroxabano
- apixaban
- edoxaban

How is the antagonizing of DOACS?

Xa inhbiitors:
- no licencesed antidote avaiable
- supportive care (transfusion red blood cells, plasma)
- potentially prothrombin concentrate

Thrombin (IIa) inhibitor (dabigatran)
- idarucizumab

Which cancer is associated with the highest risk of venous thrombosis?

hematological malignacy

Which patients with venous thrombosis are more likely to be diagnosed with cancer in the near future?

idiopathic venous thrombosiss

Is treatment of venous thrombosis in cancer patients different from patients without cancer?

Yes, first 6 months only LMWH

Several hereditary risk factors for venous thrombosis have been identified. Would you test for those defects in a patient that has developed a DVT?

What is wrong in Von Willebrands disease? Give epidemiology.

Abnormality in both primary and secondary hemostasis.
Frequency < 1 - 1%
Subdivision in types:
type 1: moderate lowering vWF
type 2: activity lower than antigen level
type 3: severe form
Normandy: less binding of factor VIIIc
Autosomal inheritance: men and women equally affected

What is the clinical presentation of VWD?

Skin and mucosal bleeding
Nose bleeds
Menorrhagia
Bleeeding after trauma and surgery
Much less muscle and joint bleeds

In general a much less severe bleeding tendency than hemophilia

What is the difference between hemophlia A and B?

Hemophilia A: shortage of coagulation factor VIII
Hemophilia B: shortage of coagulation factor IX

No difference in clinical presentation between A and B
Frequency in 1: 10.000 in the Netherlands around 1500 patients

X-linked hereditary disease: Men are affected, woman are carriers

What symptoms in mild, moderate severe and severe hemophilia?

Mild: bleeding after trauma and surgery
Moderate severe: bleeding after trauma and surgery, sometimes spontaenous bleeding
Severe: bleeding after trauma and surgeyr, spontaenous bleeding

Repeated bleeding in msucles and joints leads to joint damage and severe disability

A 20 year old woman with VWD type 1 needs extraction of a wisdom tooth. How would you treat her to prevent bleeding during surgery?

Test effectiveness of DDAVP, than DDAVP together with tranexamic acid

A 13 month old boy with severe hemophilia A presents with a bleed in his right knee. How to treat him?

Recombinat clotting factor VIII

How do you treat VWD?

DDAVP: release from VWF and FVIII from weibel-palade bodies. Depends on type VWD, not in type 2b, always to be tested

Clotting factor concentrate: intermediate purity factor VIII concentrate, contains both VWF and factor VIIIIc

Plasma dervied
recombinant conentrate is available
tarnexamic acid: inhibits fibrinoolysis

What is the mode of action of tranexamic acid?

You have lysine binding sites at plasminogen.
Tranexamic acid is a lysine analogue, which binds to those binding sites.
Thereferore there will not be fibrin degradaation, since plasminogen can't bind to fibrin.

How to treat hemophili?

Concentrates of factor VIII or X
Plasma derived or made by recombinant DNA techniques
prophylactically or on demand

What are side effects of DDAVP?

Headache, flushing, hypotension, fluid retention, hyponatremia.

What are side effects of factor concentrates?

allergic reactions: fever, urticaria, glottic oedema, anaphylactic shock, dizziness, nausea

Development of antibodies against the factor, inhibitor
Viral infections int he past: hepatitis A, b, c, hiv

What are vitmin K antagonists?

Vitamin K antagonists are used for the prevention and treatment of arterial and venous thrombotic disease.
In the netherlands phenprocoumon and acenocoumara..

There is a small therapeutic index.
The difference in the anticoagulant effect between thrombosis and bleeding is small.
Treatment with VKA has to be monitored with measurement of the INR.

The VKA inhibit the recyclling of vitamin K in the liver during syntehsis of vitamin K dependent clotting factors II< VII< IX< X

What can you do when you have bleeding dure to VKA?

skipping the VKA medication
small amount of oral vitamin K
vitamin K IV
prothrombin complex concentrate (II, VII, IX, X)

life threatening:
- c10 mg vitamin K intravenously
- prothromboin complex concentrate, dosage dpending on the INR and body weight

How to treat a bleed in DOAC use, XA inhibitors

stop the drug
give prothrombin complex
if not effective give FEIBA or NOvoseven

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MOD2

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