fVIII : x U/kg will raise activity level by 2%
give 15U/kg, 25U/kg, or 50U/kg for mild, mod, severe bleeding
give FFP if VIII not available; FFP has ~300U of fVIII; need more than ~12U FFP for severe in 70kg pt (5L)!
alternatively give cryo which has 150U fVIII; need 24U for severe in 70kg patient (750mL)
fIX : x U/kg will raise activity by 1%
give 20U/kg, 25U/kg or 50U/kg for mild, mod, severe bleeding
give FFP if fIX not available; 1U FFP raises by ~3%; need about 17U FFP for severe; cryo will not work
DDAVP effective in type I (most common)
fVIII has most vWF and preferred in type II and III (rare types)
cryo and FFP effective for all types
Clotting is a complex interplay between the level and activity of coagulation factors, fibrinogen, platelets, and plasminogen. In bleeding patients, it is important to perform hemostatic resuscitation and focus on repleting any deficits in the above products. Unfortunately, the conventional tests of coagulopathy poorly assess coagulation as a whole. PT and PTT are useful when monitoring for drug effects but are not great in guiding transfusions because the tests are in vitro and not physiologic. Despite this, we heavily utilize these tests as an indicator for transfusion with FFP.
The problem with FFP is that it has lost most its factor activity from the freezing and thawing process; each unit contains only 5-10% of active factor function. Additionally, FFP contains proteins C and S which can induce a coagulopathic state. Attempts to normalize INR with FFP is very difficult unless exorbitant volumes of FFP are given. In fact, studies have shown that below 1.7, FFP does not decrease INR any more than placebo.
Change in INR with FFP (white bars) and without FFP (black bars)
If you truly believe in your INR value and wish to resuscitate with FFP, change in INR after 1U FFP = 0.37 x pretransfusion INR – 0.47. I use the table below as a heuristic to guide transfusion requirements.
The conventional coagulation cascade is complex and of little clinical relevance because there is too much tribute to individual coagulation factors. We do not replete individual coagulation factors nor do we check them when making urgent/emergent clinical decisions.
I use a more pragmatic hemostasis cascade when considering the actively bleeding patient.
Injury, stress, or trauma exposes vWF, which binds collagen to platelets. Activated platelets recruits other activated platelets forming the platelet blanket – I use this term because platelets activation is akin to parachute deployment under electron microscope. Coagulation factors are also activated in this milieu and reinforces the platelet blanket, creating the platelet plug. Coagulation factors culminates in catalyzing fibrinogen to fibrin. Fibrin matures this plug into clot and determines the ultimate strength of this conglomeration. The body puts a stop to this positive feedback cycle by introducing plasminogen/plasmin homeostasis.
- Platelets get activated and make a platelet blanket
- Platelet blanket gets sticky because coagulation factors bind them together creating the platelet plug
- Platelet plug in turn recruits fibrin which contracts down and makes clot
- Clot gets stabilized/destabilized by plasminogen/plasmin homeostasis
Thomboelastography (TEG) can measure the activity of most of these processes, which is valuable because the levels very poorly reflect function. TEG starts with whole blood in citrate warmed to 37deg. Kaolin and sometimes tissue factor are used as activators. This vial is oscillated slowly around a submerged torsion pin to simulate venous blood. Initially the torsion pin moves freely because the blood does not pose enough inertia to drag the pin. As clots start to form, the viscosity of blood changes and drags the pin. The amplitude of pin movement reflects the relative strength of the clot and is plotted against time to form this graph:
There are several important variables: