Indolent cancers are usually not responsive to chemotherapy because
the cells do not divide but cancers are targeted when they divide. As
such, the new therapy is the monoclonal antibodies.
ALWAYS GIVE PPI (OMEPRAZOLE) when giving dexamethasone to
provide protective effect against dexamethasone induced gastric
mucosal damage and ulcers!
Prednisolone/steroids can cause neutrophilia because steroids reduce
the adherins around neutrophils, causing them to be less sticky (makes
sense since they will suppress inflammatory response). Thus, more
neutrophils are present in the blood.
Monocyte is in Blood vessel, macrophage is in tissues and histiocytes
are those that stay long in the tissue
Alcohol can cause CLD and hence cause pancytopenia or a direct
suppression effect on the BM
In cancers, warfarin is a contraindication. Use Clexane for DVT
prophylaxis or therapeutic DVT doses instead of NOACs. Evidence is
better for subcut clexane
• Check anti-Xa levels about 4h after dose of clexane
Ca2+ is an important ion needed for the coagulation cascade.
• EDTA tube (Citrate) is a calcium chelator and hence will not allow
for coagulation
• Citrate is also used for regional anticoagulation in dialysis
patients
• Calcium choride also has vasoconstiction effect which helps to
increase BP
FFP has factors 2, 7, 9, 10
Prothrombinex has factors 2, 9, 10 (DON'T HAVE 7)
§ Note that all anticoagulants do NOT actually breaks down clots, but only prevent the
propagation of the clot and prevents new ones from forming!
• Main purpose of somatic hypermutation in B cells: generate receptor diversity
For transplants:
• ABO, Rh blood antigen, HLA-A, -B, -DR, -DQ, -DO, -DP, -DM most important
3 tests mainly done:
• Blood typing
o Do note that the universal donor and recipient of different blood groups
will vary according to WHAT product you are giving, If giving packed
red cells, O is the universal donor and AB is universal recipient. If
giving plasma, AB is the universal donor and O is the universal
recipient
• HLA typing
• Cross match typing
,Dabigatran Apixaban Rivaroxaban
Direct IIa inhibitor Direct Xa inihibtors Direct Xa inhibitors
Monitor: dilute thrombin Monitor: Anti Xa apixaban Monitor: Anti Xa
time assay rivaroxaban assay
Coagulation cascasde
Think in 2 ways:
1. PTT pathway: Intrinsic + common pathway
2. PT pathway: extrinsic + common pathway
Common pathway: (All denomination under $20): Factor I, II, V, X
Intrinsic pathway: (All factors between 8 and 12): Factor VIII, IX, XI, XII
Extrinsic pathway: Factor VII (tissue factor: factor III is made by damaged cells)
• aPTT: Assess deficiencies of intrinsic pathway + common pathway factors
, • PT: Assess deificiencies of extrinsic pathway + common pathway factors
• INR: derived from ratio of Patient PT: mean normal PT
• TT (thrombin time): Deficiencies of fibrinogen or inhibitors to thrombin
• Anti-Xa (Done 4h post dose): Accurate measurement of anticoagulant activity
(heparin, LMWH, fondaparinux or direct Xa inhibitors)
• D-dimer: breakdown products by the breakdown of clots (D-dimer contains 2 cross-
linked D fragments). Elevated D-dmier is NOT specific to thrombosis. May be
assoiated with non-specific diseases or inflammatory states (recent surgery, cancer,
infection, DIC, pregnancy)
Types of anticoagulants:
• Unfractionated heparin: binds to antithrombin (previously known as antithrombin III)
o Inhibits factor 2, 9, 10, 11, 12
o Monitor using aPTT or anti-Xa
o Half life: 60-90 mins IV, slightly longer for subcut
o Antidote: protamine
• LMWH: binds to antithrombin
o Inhibits factor 2, 10
o Acts on common pathway and hence monitor/measure using anti-Xa levels
o Half life: 3-6 hours (renally cleared, hence prolonged if renal failure
o No specfic antidote but can use protamine
• Warfarin: vitamin K antagonist
o Inhibits factor 2, 7, 9, 10 and natural anticoagulants (protein C and S)
o Monitor using PT and INR
o Half life: 36-42 hours
• Direct Xa inhibitors
o Directly inhibit factor 10
o Monitor using anti-Xa assay
o Half life:
§ Apixaban 7-8 hours
§ Rivaroxaban: 11-13 horus
o Antidote: Andexanet alfa (recombinant Xa protein)
• Direct IIa inhibitors
o Directly inhibit factor 2
o Monitor using TT (normal TT suggest minimal or no plasma dabigatran) since
aPTT, PT and INR will be affected by other pathways
o Other IV agents: bivalirudin, lepirudin, argatroban (All used in heparin
induced thrombocytopenia)
o Half life (dabigatran): 12-18 hours and renally cleared
o Antidote: Idarucizumab
INR≥1.5 with life • Cease warfarin
threatening bleed • Vitamin K 5-10mg IV
including intracranial • Admit to hospital
bleed • Prothrombinex (Factor 2,9,10 conc) 50 units/kg (lower does if
INR 1.5-1.9
• FFP 150-300ml (1-2 units)
INR≥2.0 with • Cease warfarin
clinically significant • Vitamin K 5-10mg IV
but not life • Admit to hospital
threatening bleed • Prothrombinex: 35-50units/kg according to protocol
Any INR with minor • Omit warfarin, repeat INR the following day and adjust dose
bleed • If bleeding risk is high or INR >4.5, consider vitamin K 1-2mg
PO or 0.5-1mg IV
INR < 4.5 with no • Lower dose or omit warfarin
bleeding • If above by 10%, no adjustment is required
INR 4.5-10 with no • Cease warfarin
bleeding • Consider reasons for high INR and measure
, • If high bleeding risk: Vitamin K 1-2mg PO or 0.5-1mg IV
• Measure INR in 24h and readjust dose
INR >10 with no • Cease warfarin and measure INR
bleeding • Vitamin K 3-5mg PO or IV
• Measure INR in 24h and every 1-2d for 1 week
• Resume warfarin
• If high bleeding risk, can consider prothrombinex 15-
30units/kg
High risk of bleeding:
• Major bleed in last 4 weeks
• Major surgery within last 2 weeks
• Platelet count < 50
• Liver disease
• Concurrent antiplatelet therapy
1. Vitamin K1 phytomenadione
o Oral: 24h to reverse
o IV: 6-8h to reverse
o View this as a “modified release” drug for longer acting effect
2. Prothrombinex: freeze dried powder containing factor 2, 9, 10, antithrombin and
heparin
o Used when rapid correction is necessary
o Reconstituted into small volume for rapid infusion nad fast onset of action
3. FFP: contains ALL coagulation factors in blood
o Due to freezing storage requirement, takes ~30mins to thaw
o Indications:
§ If vitamin K or factor concentrate are not available
§ Patients requiring replacement of coagulation factors
§ Warfarin overdose with life threatening bleed in addition to
prothrombinex and vitamin K
§ TTP
Cause Factors affected
Heparin Prevents activation factors 2,9,10,11
Warfarin Affects synthesis of factors 2,7,9,10
DIC Factors 1,2,5,8,11
Liver disease Factors 1,2,5,7,9,10,11
Interpretation blood clotting test results
Disorder APTT PT Bleeding time
Haemophilia Increased Normal Normal
von Willebrand's disease Increased Normal Increased
Vitamin K deficiency Increased Increased Normal
the cells do not divide but cancers are targeted when they divide. As
such, the new therapy is the monoclonal antibodies.
ALWAYS GIVE PPI (OMEPRAZOLE) when giving dexamethasone to
provide protective effect against dexamethasone induced gastric
mucosal damage and ulcers!
Prednisolone/steroids can cause neutrophilia because steroids reduce
the adherins around neutrophils, causing them to be less sticky (makes
sense since they will suppress inflammatory response). Thus, more
neutrophils are present in the blood.
Monocyte is in Blood vessel, macrophage is in tissues and histiocytes
are those that stay long in the tissue
Alcohol can cause CLD and hence cause pancytopenia or a direct
suppression effect on the BM
In cancers, warfarin is a contraindication. Use Clexane for DVT
prophylaxis or therapeutic DVT doses instead of NOACs. Evidence is
better for subcut clexane
• Check anti-Xa levels about 4h after dose of clexane
Ca2+ is an important ion needed for the coagulation cascade.
• EDTA tube (Citrate) is a calcium chelator and hence will not allow
for coagulation
• Citrate is also used for regional anticoagulation in dialysis
patients
• Calcium choride also has vasoconstiction effect which helps to
increase BP
FFP has factors 2, 7, 9, 10
Prothrombinex has factors 2, 9, 10 (DON'T HAVE 7)
§ Note that all anticoagulants do NOT actually breaks down clots, but only prevent the
propagation of the clot and prevents new ones from forming!
• Main purpose of somatic hypermutation in B cells: generate receptor diversity
For transplants:
• ABO, Rh blood antigen, HLA-A, -B, -DR, -DQ, -DO, -DP, -DM most important
3 tests mainly done:
• Blood typing
o Do note that the universal donor and recipient of different blood groups
will vary according to WHAT product you are giving, If giving packed
red cells, O is the universal donor and AB is universal recipient. If
giving plasma, AB is the universal donor and O is the universal
recipient
• HLA typing
• Cross match typing
,Dabigatran Apixaban Rivaroxaban
Direct IIa inhibitor Direct Xa inihibtors Direct Xa inhibitors
Monitor: dilute thrombin Monitor: Anti Xa apixaban Monitor: Anti Xa
time assay rivaroxaban assay
Coagulation cascasde
Think in 2 ways:
1. PTT pathway: Intrinsic + common pathway
2. PT pathway: extrinsic + common pathway
Common pathway: (All denomination under $20): Factor I, II, V, X
Intrinsic pathway: (All factors between 8 and 12): Factor VIII, IX, XI, XII
Extrinsic pathway: Factor VII (tissue factor: factor III is made by damaged cells)
• aPTT: Assess deficiencies of intrinsic pathway + common pathway factors
, • PT: Assess deificiencies of extrinsic pathway + common pathway factors
• INR: derived from ratio of Patient PT: mean normal PT
• TT (thrombin time): Deficiencies of fibrinogen or inhibitors to thrombin
• Anti-Xa (Done 4h post dose): Accurate measurement of anticoagulant activity
(heparin, LMWH, fondaparinux or direct Xa inhibitors)
• D-dimer: breakdown products by the breakdown of clots (D-dimer contains 2 cross-
linked D fragments). Elevated D-dmier is NOT specific to thrombosis. May be
assoiated with non-specific diseases or inflammatory states (recent surgery, cancer,
infection, DIC, pregnancy)
Types of anticoagulants:
• Unfractionated heparin: binds to antithrombin (previously known as antithrombin III)
o Inhibits factor 2, 9, 10, 11, 12
o Monitor using aPTT or anti-Xa
o Half life: 60-90 mins IV, slightly longer for subcut
o Antidote: protamine
• LMWH: binds to antithrombin
o Inhibits factor 2, 10
o Acts on common pathway and hence monitor/measure using anti-Xa levels
o Half life: 3-6 hours (renally cleared, hence prolonged if renal failure
o No specfic antidote but can use protamine
• Warfarin: vitamin K antagonist
o Inhibits factor 2, 7, 9, 10 and natural anticoagulants (protein C and S)
o Monitor using PT and INR
o Half life: 36-42 hours
• Direct Xa inhibitors
o Directly inhibit factor 10
o Monitor using anti-Xa assay
o Half life:
§ Apixaban 7-8 hours
§ Rivaroxaban: 11-13 horus
o Antidote: Andexanet alfa (recombinant Xa protein)
• Direct IIa inhibitors
o Directly inhibit factor 2
o Monitor using TT (normal TT suggest minimal or no plasma dabigatran) since
aPTT, PT and INR will be affected by other pathways
o Other IV agents: bivalirudin, lepirudin, argatroban (All used in heparin
induced thrombocytopenia)
o Half life (dabigatran): 12-18 hours and renally cleared
o Antidote: Idarucizumab
INR≥1.5 with life • Cease warfarin
threatening bleed • Vitamin K 5-10mg IV
including intracranial • Admit to hospital
bleed • Prothrombinex (Factor 2,9,10 conc) 50 units/kg (lower does if
INR 1.5-1.9
• FFP 150-300ml (1-2 units)
INR≥2.0 with • Cease warfarin
clinically significant • Vitamin K 5-10mg IV
but not life • Admit to hospital
threatening bleed • Prothrombinex: 35-50units/kg according to protocol
Any INR with minor • Omit warfarin, repeat INR the following day and adjust dose
bleed • If bleeding risk is high or INR >4.5, consider vitamin K 1-2mg
PO or 0.5-1mg IV
INR < 4.5 with no • Lower dose or omit warfarin
bleeding • If above by 10%, no adjustment is required
INR 4.5-10 with no • Cease warfarin
bleeding • Consider reasons for high INR and measure
, • If high bleeding risk: Vitamin K 1-2mg PO or 0.5-1mg IV
• Measure INR in 24h and readjust dose
INR >10 with no • Cease warfarin and measure INR
bleeding • Vitamin K 3-5mg PO or IV
• Measure INR in 24h and every 1-2d for 1 week
• Resume warfarin
• If high bleeding risk, can consider prothrombinex 15-
30units/kg
High risk of bleeding:
• Major bleed in last 4 weeks
• Major surgery within last 2 weeks
• Platelet count < 50
• Liver disease
• Concurrent antiplatelet therapy
1. Vitamin K1 phytomenadione
o Oral: 24h to reverse
o IV: 6-8h to reverse
o View this as a “modified release” drug for longer acting effect
2. Prothrombinex: freeze dried powder containing factor 2, 9, 10, antithrombin and
heparin
o Used when rapid correction is necessary
o Reconstituted into small volume for rapid infusion nad fast onset of action
3. FFP: contains ALL coagulation factors in blood
o Due to freezing storage requirement, takes ~30mins to thaw
o Indications:
§ If vitamin K or factor concentrate are not available
§ Patients requiring replacement of coagulation factors
§ Warfarin overdose with life threatening bleed in addition to
prothrombinex and vitamin K
§ TTP
Cause Factors affected
Heparin Prevents activation factors 2,9,10,11
Warfarin Affects synthesis of factors 2,7,9,10
DIC Factors 1,2,5,8,11
Liver disease Factors 1,2,5,7,9,10,11
Interpretation blood clotting test results
Disorder APTT PT Bleeding time
Haemophilia Increased Normal Normal
von Willebrand's disease Increased Normal Increased
Vitamin K deficiency Increased Increased Normal
