Week 143 Haemostasis Flashcards
42 yr old man with recurrent epistaxis (since teens), with subsequent iron deficiency, and required blood transfusions on occasions.
A family history (father and sister) of nose bleeds. O/E severe lesions on lips and tongue of dilated blood vessels. Nml plt, Nml coag. It’s??
Hereditary haemorrhagic talengectasia.
Autosomal dominant condition.
What is normal haemostasis
quick, efficient, clot formation at the site of a bleed.
7 Y/O girl chest infection 7/7 ago. Purpura (petichae) on body, particular legs, no meds, no other sig. history. O/I All normal, except low platelet count., blood film = isolated thrombocytopenia. This is likely to be________.
Immune thrombocytopaenia.
5/12 YO baby with swollen painful Rt knee. knee bent and stiff, no history of trauma, normal birth, no fmh. IVX show FBC normal, coagulation = Factor VII > 2%. It is likely _________.
Severe Haemophilia A.
75 yo woman, collapsed at home. Morning malaena. PMH - AF on long term therapy.
O/E = pale, BP 90/60, PR 124/min
Coagulation - INR 8 (target 2-3) This is likely ______ due to ______.
GI bleed due to warfarin od.
In deranged haemostasis there is:
Abnormal bleeding (excessive prolonged or delayed)
Non-physiological thrombosis
Primary haemostasis is __________.
The formation of a platelet plug.
Secondary Haemostasis is __________.
The formation of a fibrin clot.
Plasminogen becomes Plasmin via ______. Plasmin then cleaves Fibrin to form ________. This process can be investigated with the ______ Test.
Tissue plasminogen activator
Fibrin degradation products
D-Dimer test.
Failure of haemostasis means ____ or ______.
Bleeding or pathological thrombosis.
Platelets recognise (using glycoprotein 1b/1x/v) VWF (vonwilemhalm factor???) to recognise ______.
Areas of damaged endothelium.
Which glycoprotein on a platelet binds to vWF?
GP1b
What is a tissue factor?
A Factor released from damaged tissue.
The extrinsic pathway of coagulation comes from ______.
Tissue factors.
The intrisic coagulation cascade is initiatedb y ______.
Phospholipid surface.
To convert prothrombin to thrombin from the common pathway you need_________.
Factor Ten (FX) + Factor Five a (FVa) + PLCa2+.
The test for the extrinsic pathway is called the _______.
The prothrombin time, normalised with INR.
In extrinsic, to activate the normal pathway ________ is formed.
Tissue Factor/FVIIa
To test the final pathway, you add ______ and assess the ______.
Thrombin, and assess clot formation time.
To test intrinsic factor, you use __________.
Activated partial thromboplastin time (APTT).
Intrinsic factors are _______—–>_________—–> _________——-> ___________, which activates normal pathway.
FX11–> FX11a –> FX1a –> FIXaFV111a, PLCa2+
Site of bleeding for primary haemostasis is _____.
Skin, mucous membranes.
Primary haemostasis presents with which symptom?
Petichae
In secondary haemostasis, petichae is _____ _______.
Not present.
Echymoses means _____. In secondary haemostasis, these are _____. In primary haemostasis these are ___ and ____.
Bruise
Large, palpable
Small, superficial
Haemoarthroses/muscle haematomas are ____ in primary and ____ in secondary haemostasis.
Rare in primary
Common in secondary
Bleeding after surgery is ___ and ____ in ______, and _____ and _____ in ______haemostasis.
Immediate and mild in primary
Delayed and severe in secondary
What two reasons will a patient present with purpura?
thrombocytopaenia - most common cause for sepsis –> if platelet count is low, likely cause.
OR
vasculitis (if platelet count is normal) i.e. Henoch-Schonlein purpura
Henoch-Schnoleein purpura is a form of ______.
Vaculitis
Glanzmann’s thrombasthenia is a lack of _____ normally presenting in neonates.
GPIIb/IIIa
Vitamin K is needed to make Factors _______ (4 of them).
2, 7, 9, and 10.
Defective haemostasis will present with a history of:
Abnormal bruising, prolonged bleeding from cuts, nose bleeds, menorrhagia, bleeding after child birth, dental history, bleed post-surgery, previous anaemia and transfusion, drug history and family history.
FBC will detect ____.
Anemia; Red cell fragmentation.
THROMBOCYTOPAENIA
APPT (ACTIVATED PARTIAL THROMBOPLASTIN TIME) DETECTS WHAT?
DEFICIENCY OF ALL COAGULATION FACTORS (EXCEPT VII)
HEPARIN
INR (ONE STAGE PROTHROMBIN TIME) WILL DETECT WHAT?
DEFICIENCY OF FACTORS I, II, VII, AND X.
THINK = WARFARIN
FIBRINOGEN OR THROMBIN CLOTTING TIME WILL DETECT WHAT?
REDUCED OR ABNORMAL FIBRINOGEN. HEPARIN; FIBRIN DEGRADATION PRODUCTS.
BLEEDING TIME (NOT TO BE DONE IF THROMBOCYTOPAENIA) DETECTS WHAT?
TEST PLATELETS - VESSEL WALL INTERACTION.
THE SPECIAL TEST OF MIXING TESTS WITH NORMAL PLASMA WILL DO WHAT?
ASSESS IF NORMAL PLASMA CORRECTS PROLONGED APTT AND OSPT.
COAGULATION FACTOR ASSAYS ARE USED TO DO WHAT?
ASSESS/CONFIRM COAGULATION FACTOR DEFICIENCY.
VON WILLIBRAND FACTORS ASSAYS DO WHAT?
HELP CONFIRM VW DISEASE, IF SUSPECTED.
FACTOR VII/OTHER IHIBITO ASSAY IS CONDUCTED IF?
IF YOU SUSPECT ANTIBODY BEING PRODUCED TO COAGULATION FACTOR.
PLATELET FUNCTION TESTS TEST _____.
QUALITATIVE PLATELETS DEFECTS.
BERNARD-SOULIER DISEASE IS DEFINED AS A LACK OF ____.
GPIb
Will see thrombocytopenia +platelet dysfunction + AB
Essential requirements of normal haemostasis are:
Normal blood vessels
Adequate platelet number and fuction
Normal coagulation system
Normal and effective fibrinolytic system
Auto-immune thrombocytopaenia is _____. Platelet lifespan is ____ from ____ to a _____.
Immunological destruction of platelets.
Lifespan reduced from 7-10 days to a few hours.
Destroyed in spleen and liver
Can be acute OR chronic
Inherited coagulation disorders include:
Haemophilia A - Factor VIII def
Haemophilia B - Christmas disease - IX Def
Von Willebrand - Von willebrand factor
Most common cause of low platelets is?
Thrombocytopaenia.
Purple tops used for?
FBC
BLUE TOP MUST BE FILLED TO WHAT?
THE LINE!!!!!
PROTHROMBIN TIME IS USED TO CALCULATE WHAT?
INR (WARFARIN MORNITORING)
WHAT ARE THE COMPONENTS OF THE HAEMOSTATIC SYSTEM?
PLATELETS
PROTEINS - VWF
DAMAGED ENDOTHELIUM – PHOSPHOLIPIDS, COLLAGEN, VWF, TF
WHERE DO PLATELETS COME FROM?
ORIGANATE FROM MEGAKARYOCYTES (FROM MYELOID PROGENITOR LINEAGE) IN THE BONE MARROW.
BUDS OF GRANULAR CYTOPLASM (CONTAIN CLOTTING FACTORS).
WHERE DOES FIBRIN COME FROM?
FIBRINOGEN - CONVERTED TO FIBRIN BY THROMBIN
THIS IS CAUSED BY CLOTTING CASCADE (EXTRINSIC/INTRINSIC)
LIVER DAMAGE WILL RESULT IN (MOST LIKELY)
REDUCTION IN FIBRINOGEN AND CLOTTING FACTORS - LIVER MAKES A LOT OF PROTEINS!
PLATELET PHOSPHOLIPID BILAYER DOES WHAT?
EVERTS TO PRESENT A HUGE PHOSPHOLIPID MEMBRANE SURFACE AREA, IN ORDER TO ACTIVATE PROTEINS.
HOW DOES WARFARIN WORK?
IT IS A DIRECT INHIBITOR OF VITAMIN K (COMPETITIVE INHIBITION), STOPPING ACTIVATION OF VIT K DEPENDENT FACTORS.
WHAT COULD YOU GIVE TO REVERSE THE EFFECTS OF WARFARIN?
PROTHROMBIN COMPLEX CONCENTRATE (PCC) - VIT K DEPENDENT FACTORS
VITAMIN K - SLOWER (OVER 24 HOURS)
WHAT IS HEPARIN? HOW DOES IT WORK?
ANTICOAGULANT AGENT
?????
WHAT IS ASPIRIN? HOW DOES ASPIRIN WORK?
IT IS AN SALICYLATE ANTICOAGULANT. IT INHIBITS PLATELET ACTIVATION.
WHAT FACTORS MAKE BLOOD MORE LIKELY TO BE LIQUID?
???
WHAT FACTORS MAKE BLOOD MORE LIKELY TO BE SOLID
???
WHAT DRUGS INFLUENCE PLATELET FUNCTION AND WHY?
????
What does virchow’s triad include?
Vessel wall damage (i.e. atherosclerosis)
Altered Blood flow (i.e. stasis)
Increased blood coagulability (i.e. thrombophilia)
Define placebo.
A substance or procedure that has no inherent power to produce an effect that is sought or expected.
What is a thrombus?
A clot arising in the wrong place.
Naturally occuring inhibitors of blood coagulation are ____ and ______.
- Anti Thrombin
- Protein C System (protein s)
What is antithrombin?
- A glycoprotein
- synthesised by liver
- Inhibits FXa and thrombin
- > 2000 fold increase of the T/AT interaction by heparin
There is a dose response curve for the ______ _______.
Placebo effect.
Which vitamin is vital for coagulation?
Vitamin K
Thrombomodulin is linked to which vitamin?
Vit K
The protein C system inhibits ______
Va -> VIIIa
What three types of thrombus are there?
Arterial
Venous
Microvascular
Arterial thrombus is described as a ____ ______. They are made of ______ and ______. They result in _____ and ______, and principally secondary to _______________.
White clot
Platelets and fibrin
Ischaemia & Infarction
Atherosclerosis
Name three types of arterial thromboembolism.
Coronary (Mi/Angina)
Cerebrovascular (stroke/transient ischaemia)
Peripheral embolism (Limb ischaemia)
Describe microvascular thrombus.
Platelets and/or Fibrin
Results in diffuse ischaemia
Principally in DIC
Venous thrombus is describes as a ____ ______. It is made up of ____ and ___ ______ cells. It results in back _____. It is principally due to ____ and ______.
Red thrombus
fibrin and red blood cells
Results in back pressure
due to stasis and hypercoagulability
What is the extinction of an association?
The overwriting of pavlovian conditioning. It’s NEW learning.
Name two important examples of venous thromboemoblism.
Limb deep vein thrombosis
Pulmonary embolism
Name as many risk factors for venous thromboembolism as you can.
Immobility Tissue trauma (surgery) Pregnancy Oral CCP Obesity MAlignancy Hyperviscosity Anti-phospholipid syndrome
A variant in TPH2 predicts what?
Whether ppl with social anxiety disorder will experience a placebo effect or not.
What is Factor V Leiden?
A common heritable thrombophilia.
5% caucasians
7 fold increase of VTE
40 x increase risk in oral contraceptive
Name two common heritable thrombophilia?
Factor V Leiden
Prothrombin G20210A
Name 3 rare causes of heritable thrombophilia.
Antithrombin deficiency
Protein C Deficiency
Protein S deficiency
What are the clinical diagnostic criteria for antiphospholipid syndrome?
Vascular thrombosis
Complications of pregnancy:
- 3 or more unexplained consecutive abortions <10w
- 1 or more loss after 10w
- 1 or more unexplained premature birth Up to 34 w
What are the laboratory diagnostic criteria for antiphospholipid syndrome?
Anticardiolipin antibodies IgG or IgM
Lupus anticoagulant
Diagnosis req’s at least 1 clinical and 1 laboratory confirmed x2
The full effect of a drug is:
Placebo + Natural history + Drug
What laboratory test would you do to confirm DVT? How would you confirm it?
D-Dimers
Imaging to confirm (uS)
3 or more of WHAT will give high probability of DVT potential?
Active Cx in last 6/12 Paralysis Bad >3d Swollen leg/calf swolllen > 3cm/Pitting odemea Tenderness along veins
What is the nocebo effect?
Same principle as placebo effect, except that outcome is negative.
< anxiety contributes to this.
Describe DVT prophylactic treatment.
MObility, hydration
TED stocking, pneumatic compression
Heparin, i.e. LWMH/other agents
What is the Hawthorne effect?
An increase in worker productivity produced by the pysch stimulus of being singled out and made to feel important.
Unfractionated heparin inactivates what?
IIa and xa
What is the difference in molecular weight between UFH and LMWH?
UFH = 15 LMWH = 4.5
What is the difference in half life between UFH and LMWH?
UFH = 2 hours LMWH = 4-8 hours
When should you suspect pulmonary embolism?
- Always in sudden collapse 1-2 weeks after surgery
- Dyspnoea at rest or with exertion (usually in seconds or minutes)
- Pleuritic pain
- cough
- Calf/thigh pain/swelling
- Wheezing
How does PE present clinically?
Tachypnea Tachycardia Rales (crackles) > breath sounds Jugular venous distension
What investigations would you conduct to diagnose a PE?
ABG ECG CXR U/S lower limbs D-Dimers
What is a CT-PA?
83% of patients with PE had a positive scan.
96% without had a negative scan
What is a V/Q scan?
A normal scan virtually excludes PE
HIgh probability and clinical sign –> 95% likelihood of PE.
What is the gold standard for PE?
Pulmonary angiography.
2% mortality
5% morbidity
How would you manage a PE?
Resucitation Anti-coagulation -----> IVC filters when this is contra indicated -LMWH - Warfarin Thrombolysis,
Describe the extrinsic coagulation pathway.
VII + Tissue factor –> VIIa/TF
VIIa/TF ——-Va——–> changes x –> Xa
Xa changes Prothrombin —> Thrombin
Thrombin changes Fibrinogen —-> Fibrin
Describe the intrinsic coagulation pathway.
XII—->X11A CAUSES..
X1—->X1A CAUSES…
IX —->IXA CAUSES…
THEN IXa—-> to X (then goes from there…)
THROMBIN CAUSES A _____ FEEDBACK LOOP
POSITIVE
DESCRIBE THE CASCADE OF FIBRINOLYSIS.
UROKINASE TPA TURNS PLASMINOGEN INTO PLASMIN
PLASMIN THEN TURNS FIBRIN INTO FIBRIN DEGRADATION PRODUCTS
WHAT IS THROMBOCYTOPAENIA?
BASICALLY, A LOW PLATELET COUNT.
BRUISING, PETECHIA, NOSEBLEEDS, BLEEDING GUMS
WHAT IS VON WILLEBRAND DISEASE?
MOST COMMON HEREDITARY COAGULATION IN HUMANS.
NEEDED FOR PLATELET ADHESION AND BINDS FACTOR 8
SIGNS OF HEAVY BLEEDING AND BRUISING
WHAT IS HAEMOPHILIA?
POOR CLOTTING
A = FACTOR 8 DEFICIENCY
B (RARER) = FACTOR 9 DEFICIENCY
RECESSIVE SEX-LINKED X CHROMOSOME DISORDER
WHAT IS DISSEMINATED INTRAVASCULAR COAGULATION?
ABNORMAL CLOTTING, CAUSING DISSEMINATE CLOTS THROUGHOUT THE BODY, LOW FIBRINOGEN AND BLEEDING. NOT GOOD!USUALLY INITIATED BY AN UNDERLYING DISORDER.
INTRINSIC ATHWAY IS MONITORED BY?
PTT
EXTRINSIC PATHWAY IS MONITORED BY
PT
IF FDP IS HIGH, CLOTTING SYSTEM IS _____
ACTIVATING LIKE transformer on a Tuesday.
what may lead to false fdp elevation?
HEPATIC OR RENAL INJURY/DAMAGE/FAILURE
WHAT ARE SHISTOCYTES?
FRAGMENTED RED BLOOD CELLS
HOW WOULD YOU TREAT DIC?
TREAT UNDERLYING DISORDER
MAY NEED TO TRANSFUSE PLATELETS
HAEMOPHILIA IS AN ___ LINKED DISORDER
X
WHAT ARE THE TYPICAL BLEEDING SYMPTOMS OF PRIMARY HAEMOSTATIC FAILURE?
IMMEDIATE BLEEDING AFTER TRAUMA
MUCOCUTAEN
PURPURA
WHAT ARE THE TYPICAL BLEEDING SYMPTOMS OF A COAGULATION FAILURE?
DELAYED BLEEDING AFTER TRAUMA
MUSCLE AND JOINT BLEEDING
BRUISING
A HIGH APTT TIME WITH A FAMILY HISTORY MEANS WHAT?
HAEMOPHILIA
IN HAEMOPHILIA, WHICH FACTORS DO YOU REPLACE?
8 AND 9
DDAVP (INCREASED BP)
TRANEXAMIC ACID
WHAT DOES TRANEXEMIC ACID DO?
INHIBITS ACTIVATION OF PLASMINOGEN TO PLASMIN
VON WILLEBRANDS DISEASE IS AN ______ CONDITION.
AUTOSOMAL
LOW PLATELETS MEAN WHAT?
THROMBOCYTOPAENIA
LOW FIBRINOGEN, HIGH PLATELETS, AND FDPS INCREASED MEANS WHAT?
DIC
NORMAL BLEEDING TIME, < TT, FIBRINOGEN = WHAT?
LIVER DISEASE
NORMAL BLEEDING TIME, NORMAL TT, NORMAL PT, < APTT, NORMAL FIBRINOGEN = WHAT?
HAEMOPHILIA
< BLEEDING TIME, NORMAL TT, NORMAL PT, <APTT AND NORMAL FIBRINOGEN = WHAT?
von willebrand disease
< TT, < PT, < APTT, >Fibrinogen = what?
DIC
<bleeding time, Normal TT, Normal PT, Normal APTT, Normal Fibrinogen =
thrombocytopaenia
what are hirudins?
antithrombins
WHAT IS THE MAIN SIDE EFFECT OF HEPARIN?
HEPARIN INDUCED THROMBOCYTOPENIA
HIT IS BROKEN DOWN INTO TWO TYPES - WHAT ARE THEY?
TYPE 1 - NON IMMUNE
TYPE 2- IMMUNE –> CAN BE DEVASTATING
HOW DOES HIT WORK?
CAUSES PLATELET REMOVAL BY SPLENIC MACROPHAGE
HOW DO YOU MANAGE HIT?
DISCONTINUE ALL HEPARIN IMMEDIATELY
AVOID PROPHYLACTIC PLATELET TRANSFUSIONS
MONITOR FOR THROMBOSIS
CONSIDER ALTERNATE COAGULATION
WHAT IS FONDAPARINUX?
SIM, TO LMWH
ANTI Xa ACTIVITY
WHAT ARE THE INDICATIONS FOR INDEFINITE ANTICOAGULANT THERAPY?
RECURRENT IDIOPATHIC VTE
INHERITED THROMBOPHILIA
ANTIPHOSPHOLIPID SYNDROME
MALIGNANCY
ANTIDOTE TO WARFARIN?
VITAMIN K
WHAT IS DABIGATRAN, AND WHAT ARE ITS ADVANTAGES OVER WARFARIN?
ANTI THROMBIN RAPID ONSET FIXED DOSE NO FOOD EFFECT AND FEW INTERACTIONS NO MONITORING AND SHORT OFFSET
WHAT ARE THE INDICATIONS FOR FIBRINOLYTIC THERAPY?
ARTERIAL THROMBOSIS
CORONARY THROMBOSIS
PE
MAIN SIDE EFFECT IS BLEEDING
