BLEEDING DISORDERS (SECONDARY HAEMOSTASIS) Flashcards
[INHERITED HAEMOPHILIAS]
What are the clinical features of Haemophilia A and B?
Haemarthrosis (most common, hallmark of haemophilia)
Soft tissue haematomas (e.g. muscle)
Other sites of bleeding: CNS in neonates, GI
Prolonged bleeding after surgery/ dental extractions
Female carriers can bleed after childbirth/surgery
Usually presents in childhood
- Acquired causes of factory deficiency is uncommon!
- Always consider possibility of inhibitors, including temperature dependent inhibitors
Bleeding pattern
- Superficial cuts do not bleed
- Bruising is common, nosebleeds are rare
- Spontaneous bleeding is deep, into muscles and joints
- Bleeding after trauma may be delayed and is prolonged
- Frequently restarts after stopping
How is haemophilia diagnosed?
Increased APTT, reduced factor assay %
How is haemophilia managed?
Treated with recombinant forms of FVIII and FIX
- Desired factor level 30-40% for early muscle/joint bleed, 50% for late bleed, 80-100% for ICH/intraabdominal bleed
Regular prophylaxis is also given to prevent bleeding (trough level above a certain threshold)
- 3x/week for severe haemophilia
- PRN for mild patients.
Additional haemostatic treatments: Tranexamic acid, DDAVP (for mild haemophilia A by temporarily increasing factor VIII), fibrin glue/spray.
- vWF is bound to F8, hence by giving DDAVP: F8 and vWF will increase
- Tranexamic Acid prevents fibrinolysis
Other blood products that contain Factor VIII:
- plasma
- cryoprecipitate
- factor concentrates
[Factor INHIBITOR]
There is a special class of inhibitors that is ______________
- Normal tests will reveal a pattern akin to factor deficiency aka correctable with 1:1 mixing studies
- On __________: APTT will show pattern of inhibition instead
- Of all these inhibitors, F8 Inhibitor is the most common!
Quite commonly seen 1-2 every ½ year
When will be suspect a F8 Inhibitor?
- An acquired factor deficiency is generally rare in adults – may be drug-induced however in this case will be non-correctable
- In such patients, we must always suspect possibility of an inhibitor instead, which are commonly acquired
TIME and TEMPERATURE dependent;
incubation
{factor inhibitors]
What is the management of factor inhibitors?
- Giving patients more coagulation factors will NOT help UNLESS THE INHIBITOR IS WEAK – we assess by looking at inhibitor assay
Instead, we can give (steroids OR cyclophosphamide) + (IVIG OR recombinant 7A OR activated form of PCC). o Immunosuppression takes time to work (1-2 weeks), in the meantime we can give recombinant 7a OR activated PCC OR IVIG.
Recombinant 7A: Recombinant 7A is given to directly increase thrombin production via intrinsic pathway, hence bypassing the need for adequate factors in the extrinsic pathway
Activated PCC: Contains activated Xa and IIa
[Liver disease]
The liver synthesizes almost all proteins involved in haemostasis, with exceptions being __________________. The PT is a sensitive indicator of hepatic synthetic function due to the ____________, which the failing liver cannot maintain.
The PT and aPTT are both prolonged with _______________.
Fresh frozen plasma transiently replaces all coagulation factors but is short lived.
_____________ is useful if the fibrinogen level is <100 mg/dL.
vWF and tissue plasminogen activator;
short half-life of factor VII (6 hours);
more severe hepatic synthetic dysfunction;
Cryoprecipitate
[VITAMIN K DEFICIENCY AND INHIBITION]
What are the causes of vitamin K deficiency?
- Reduced intake of dark green vegetables
- Reduced absorption: requires gut flora to metabolize Vit K into absorbable forms, hence Abx use / SIBO = reduced metabolism and absorption
- Reduced absorption: requires bile to absorb Vit K A D E, hence cholestasis / pancreatic insufficiency = reduced vit K absorption
- Vit K antagonist – i.e. Warfarin use
[VITAMIN K DEFICIENCY AND INHIBITION]
What is the management of vitamin K deficiency?
Oral/ Subcutaneous Vitamin K – Corrects clotting time within 24 hours in pt with normal hepatic function
IV vitamin K – Risk of anaphylaxis is increased.
4-Factor PCC – a quick replacement of the 4 coagulation factors required
Fresh frozen plasma is used when urgent correction is required.
[VITAMIN K DEFICIENCY AND INHIBITION]
How to correct INR in pt on warfarin?
> therapeutic limit but < 6
- Bleeding: 4 factor PCC + Vit K
- Not bleeding: Drug holiday for 1-3 days and start warfarin again subsequently
> 6
- Bleeding: 4 Factor PCC + Vit K
- Not Bleeding: Vit K replacement
- Normal INR = 1
- Target INR in pt with A-Fib –> 2.5 (hence acceptable range = 2-3)
- Target INR in pt with mechanical valve –> 3 (hence acceptable range = 2.5-3.5)
[DISSEMINATED INTRAVASCULAR COAGULATION (DIC)]
DIC is both a disorder of primary and secondary haemostasis. DIC is not a disease, and is always secondary to an underlying disorder. There is an excessive and inappropriate activation of coagulation.
- Increased used of procoagulant factors
- Increased use of inhibitory factors
- Increased clot formation
- Increased clot dissolution (fibrinolysis)
- Increased platelet consumption
Fibrin deposition within circulation leading to ORGAN DAMAGE
- Direct release of tissue factor and other procoagulants (e.g. fat, phospholipids, amniotic fluid) into circulation leads to _______________
- The release of procoagulants and tissue factor can be due to tissue trauma or malignancy.
- There might also be an increased expression of _________ secondary to endothelial damage (e.g. gram negative sepsis, burns).
- This leads to formation of _______ in the circulation, and hence the formation of microvascular thrombi. Initially, due to high levels of PAI-1, removal of fibrin is impaired.
- Microvascular occlusion leads to tissue damage in kidney (AKI), brain, heart, liver, and capillary leak in the lung, eventually leading to multi organ failure.
- Red cells get torn in the occluded blood vessels (MAHA) and are seen as _________________.
Consumption of platelets and coagulation factors leading to BLEEDING
- Due to the activation of the clotting cascade, ____________ are rapidly depleted.
- At later stages of DIC, your body will also respond by attempting to break down the excess fibrin deposits, increasing fibrinolysis.
- This contributes to bleeding at a later stage in DIC.
increased thrombin generation;
tissue factor;
fibrin
schistocytes;
platelet and clotting factors (e.g. fibrinogen)
[DISSEMINATED INTRAVASCULAR COAGULATION (DIC)]
What are the clinical features of DIC?
- Bleeding (64%)
- Change in renal panel (25%)
- Change in LFTs (19%)
- VTE (7%)
[DISSEMINATED INTRAVASCULAR COAGULATION (DIC)]
What are the causes of DIC?
- Infections: sepsis/viremia/malaria
- Malignancy: metastatic cancer/AML M3
- Obstetric: septic abortion/placental abruption/retained dead fetus/eclampsia
- Tissue necrosis: burns/ extensive trauma/liver disease
[DISSEMINATED INTRAVASCULAR COAGULATION (DIC)]
What are the investigations of DIC?
The DIC panel includes: PT / PTT, D-Dimers, Fibrinogen
Increased PT and APTT as clotting factors are reduced. PT is the most sensitive marker for DIC (i.e. 1st to change)
Decreased Fibrinogen due to widespread fibrin formation
Increased D-Dimers due to body’s attempt to break down excess fibrin deposits
Decreased platelets and haemoglobin due to MAHA
[DISSEMINATED INTRAVASCULAR COAGULATION (DIC)]
What is the ISTH score (The International Society of Thrombosis and Haemostasis)?
Is there a relevant underlying disorder?
If YES
- Low platelets (<100 = 1, <50 =2)
- Increased FDPs (moderate =2, strong =3)
- Prolonged PT (3-6s =1, >6s =2)
- Fibrinogen (<1 = 1)
Score >= 5 compatible with DIC
Score < 5: possible DIC that is non-overt / no DIC
[DISSEMINATED INTRAVASCULAR COAGULATION (DIC)]
What is the management of DIC (BCSH guidelines)?
Transfuse platelets
- Active bleeding
- High risk of bleed with plt<50 OR non-bleeding pts to keep plt>20
- Contraindicated in thrombotic thrombocytopenic purpura and heparin-induced thrombocytopenia –> can result in further thrombosis
Give FFP if bleeding + deranged clotting / require invasive procedure
- Recommended in patients with active bleeding and an International Normalized Ratio (INR) greater than 1.6.
- OR before an invasive procedure or surgery if a patient has been anticoagulated
Give PCC if FFP contraindicated e.g. severe pulmonary edema
- contains F2, F9, F10
- used to treat and prevent bleeding in hemophilia B if pure factor IX is not available
- reverses the effects of warfarin and other vitamin K antagonist anti-coagulants
Give fibrinogen concentrate (3g) or cryoprecipitate (10U) if Fib<1g that persists post FFP infusion (dose 5- 10ml/kg paeds)
- Cryoprecipitate = prepared by thawing fresh frozen plasma and collecting the precipitate, contains high concentrations of factor VIII and fibrinogen
