Coagulopathy in trauma

Rudy Alvarez, M.D.

Objectives
• How frequently is coagulopathy seen?
• Review the mechanisms of coagulopathy in trauma
• Point of care coagulation testing
Coagulopathy of trauma: mechanisms
 Trauma and coagulopathy
• Trauma is a leading cause of death and disability
worldwide.
• Hemorrhage accounts for 40% of all trauma death
• Challenging to control in presence of coagulopathy
• Leads to early termination of surgery
• Coagulation
• Activation results in systemic inflammatory response
syndrome  susceptibility to sepsis. (blood transfusions?)
• Worsens outcomes from TBI due to hemorrhage and
neuronal loss
• Acute coagulopathy seen in as many as 1 in four trauma pts and is
associated with a 4 fold increase in mortality.
• Support for treatment directed aggressive correction of coaulopathy
can lead to dramatic reductions in mortality.
• Dilutional explanations of coagulopathy in trauma:
• “Im losing blood and need more” (outdated)
• Multifactorial, several mechanisms
Direct tissue trauma and shock are the
primary factors resulting in coagulopathy
• 1. TISSUE TRAUMA: initiates coagulation and fibrinolysis
• The injury severity (crush/explosion vs stab) assoc w degree of coagulopathy.
• Mechanism: tissue damage initiates coagulation cascade as endothelial
damage is the area of injury causes exposure of submenothelial collagen and
TF.
• Hyperfibrinolysis is a direct consequence of tissue injury and shock
• 2. Shock: prime driver of early coagulopathy
• Dose dependent correlation between severity of tissue hypoperfusion and
coagulopathy.
• Pts with shock have abnormal coagulation (PT/PTT) at admission.
• Mechanism: Probably acidemia, also widespread endothelial disruption.
Interferes with coagulation proteases
• 3. Hemodilution: dilution of coagulation
factors
• During shock, decreased intravascular hydrostatic
pressure  shift of coagulation factors from
cellular and interstitial spaces, into the plasma.
• Exacerbated by IV fluid resuscitation
• Exacerbated by pRBC therapy
• Ratio of 1:1:1 red cells: plasma: platelets is
physiologically closer to whole blood
• 4. Hypothermia: inhibits coagulation
and platelet function.
• TF, FVII activity decreases linearly with
temperature
• Platelets more sensitive to hypothermia,
decreasing activation
• Decreased heat production by
underperfused muscles
• Heat loss b/c evaporation from exposed
body cavities during surgery.
• Cold IV fluids, cold blood
• Significant coagulopathy below 34C and
markedly increased mortality below 32C
• 5. Acidemia: produced by low flow shock states and excess ionic
chloride during fluid resuscitation.
• Impairs coagulation factors’
• prolongs clotting times
• Reduces clot strength
• Although it can be corrected by buffers, apparently does not correct
coagulopathy. Other mechanism?
• 6. Inflammation: trauma induces inflammation and SIRS.
• Endothelial activation and injury activates the immune system
• There is cross talk between coagulation cascade (activates complement) and
immune response.
Thromboelastography
• Hemostasis: process of clot formation
• Joint function of platelet activation to form
platelet plug and coagulation cascade
leading to clot formation
• Conventionally measured by
• Platelet count, PT, PTT, thrombin time,
fibrinogen levels and FDPs
• Test only various parts of the coagulation
cascade but in isolation and are static tests
• Rotem
• Measures whole blood coagulation and is a good global assessment of
hemostatic function
• Commonly used in OB procedures, liver transplants, cardiac surgery.
• Useful not only in bleeding patients but to prdic preop and postop
hemostasis.
• PIFA Heparin/PF4 Rapid assay for heparin induced thrombocytopenia
(HIT):
• Indication: drastic fall in platelet count and thrombosis after a few days on
heparin
• Test: FDA cleared assay screening test to detect antibody directed against
Heparin/PF4 complex
• TAT: 10 minutes, results in <1 hour.
• Accurate: >98% negative predictive value
• Cost savings: potential to save 500k to 1million in testing, pharmacy and monitoring
• Interpretation:
• Reactive/positive
• Non-reactive/negative
• Verifynow to assess reactivity to antiplatelet agents
• Indication: up to 40% of patients on antiplatelet
medications may not receive expected platelet
inhibiting effect (i.e. drug interactions/ppis, genetic,
non-compliance.)
• Test
• PRU test-ADP/P2Y12 inhibitors- measures ADP induced
aggregation in the presence of P2Y12 inhibitors (clopidogrel,
prasugrel, ticagrelor);
• Application
• Patient variability in response to ADP inhibitors
• Patients who have been given ADP inhibitors preoperatively due
to plt dysfunction.
• Standard is to stop ADP inhibitors 5-7 days prior to surgery
• 2012 STS guidelines recommend using platelet function testing to
aid in timing of surgery instead of arbitrarily waiting a prespecified
period of time..
• Conditions that can affect results
• Patients exposed to GPIIB/IIIa inhibitors within 48 hours of
epitifibatide, tirofiban
• 14 days of abciximab.
• Interpretation
• <194PRU P2Y12 inhibitor effect present
• 194-418PRU Normal platelet reactivity (off drug)
• Test
• ARU aspirin test: measures arachidonic acid
induced aggregation due to aspirin
• Interpretation
• <549: Evidence of platelet dysfunction due to
aspirin
• >550: No evidence of aspirin induced platelet
dysfunction
• Questions?
General overview of hemostasis
• Damage to vessel is repaired via hemostasis
• Via means of a thrombus/clot at injury site
• Hemostasis occurs in two stages: Primary and Secondary
• Primary hemostasis forms a weak platelet plug
• via interaction of platelets and vessel wall
• Secondary hemostasis stabilizes the platelet plug
• via coagulation cascade
Primary hemostasis
• Platelet adhesion to the disrupted vessel
• vWF binds exposed subendothelial collagen
• Platelets bind vWF using GP1b receptor
• Platelet degranulation
• ADP is released from plts which exposes GPIIb/IIIa receptors on plts
• TXA2 is synthesized and released by platelet cyclooxygenase (COX) 
aggregation
• Platelet aggregation
• Platelets aggregate at the site of injury via GPIIb/IIIa using fibrinogen from
plasma to link  plug
Disorders of primary hemostasis “plug it”
• Quantitative (ITP, MAH, TTP, HUS) or qualitative (BS, GZ, ASA)
• Clinical symptoms
• Mucosal bleeding: epistaxis, hemoptysis, hematuria, menorrhagia
• Skin bleeding: petechiae (1-2mm), purpura (>3mm), ecchymoses (>1cm)
• Tests:
• Platelet count possibly decreased, increased bleeding time, blood smear and
bone marrow bx findings
Secondary hemostasis
• Stabilizes the platelet plug via coagulation
cascade
• Cascade generates thrombin which converts
fibrinogen in the platelet plug to fibrin, which is
cross linked yielding a platelet-fibrin thrombus.
• Coagulation factors are produced by the
liver in an inactive state and must be
activated.
• Exposure to an activating substance
• 1. EXTRINSIC path: tissue thromboplastin from
damaged tissue activates factor VII
• 2. INTRINSIC path: subendothelial collagen activates
factor XII
• Phospholipid surface of platelets
• Calcium (from platelet dense granules)
Disorders of Secondary Hemostasis
• Usually a result of coagulation factors
• Clinical sx: deep tissue bleeding into muscles and joints. Re-bleeding
after surgical procedures (circumcision and wisdom teeth extraction)
• Labs:
• PT-prothrombin time measures extrinsic
• PTT- partial thromboplastin time measures intrinsic
Heparin
-Monitor with PTT
-acts on blood
-activates antithrombin,
which decreases the action
of IIa (thrombin) and factor
Xa
-Reverse with protamine
sulfate
Warfarin
-Monitor with PT/INR
-acts on Liver
-Impairs synthesis of
vitamin K dependent CF-
II, VII, IX and X. Proteins C
&S
-Reverse with vitamin K and
FFP
-Teratogenic