Symptoms 13: Bleeding

Front 1

What part of hemostasis are platelets involved in?

Back 1

Primary hemostasis

Front 2

What are the characteristics of the structure/contents of platelets?

Back 2

- Anucleate cells
- Plasma membrane contains proteins that provide platelets w/ unique characteristics
- Granules / vesicles inside cell (2 types - gray and one that contains e- dense core = black circle)
- Marginal rim of microtubules
- Membrane invaginates to form internal membrane system that makes its way through

Front 3

What do platelets do when there is damage to the endothelium?

Back 3

1. ADHESION of platelets to subendothelium through damaged endothelium
2. SECRETION of granules through surface connected cannaliculus system, which attracts other platelets to the area
3. AGGREGATION of platelets to initiate primary hemostasis to cover defect

Front 4

How do platelets mediate binding to the subendothelial structures after damage to endothelium?

Back 4

- Platelets have VWF on their surface attached via GPIb protein
- VWF then binds to collagen
- There are other integrins that can mediate binding to subendothelial structures too

Front 5

What happens when platelets are activated?

Back 5

Platelets receive biochemical signal to change shape
- Originally round → irregular → pseudopods sticking out
- Pseudopods make contact with subendothelial CT and other platelets
- Marginal rim of microtubules and contractile proteins are activated by increased Ca2+

Front 6

What are the types of platelet storage granules?

Back 6

- Dense (delta) granules
- Alpha granules
- Lysosomal (lambda) granules

Front 7

What is found in the dense (delta) granules?

Back 7

- Nucleotides: ADP and ATP
- Serotonin (vasoactive amine)
- Calcium

Front 8

What is found in the alpha granules?

Back 8

- Fibrinogen
- Factor V
- Thrombospondin
- PDGF, PF4, βTG (platelet growth factors)

Front 9

What is the action of nucleotides (ADP) on platelets?

Back 9

Agonist for platelets, causes aggregation

Front 10

What is the action of Phospholipase A in the membrane of platelets?

Back 10

Cleaves phospholipids in membrane to generate Arachidonic Acid in cytoplasm

Front 11

What happens to Arachidonic Acid in cytoplasm of platelets after being generated by Phospholipase A in the membrane?

Back 11

- Cyclooxygenase converts AA → PGG2 and PGH2
- Thromboxane Synthease converts PGG2 and PGH2 → TxA2
- Spontaneously, TxA2 converts to TxB2

Front 12

What expresses Thromboxane Synthase? Action?

Back 12

Platelets express Thromboxane Synthase, which converts PGG2 and PGH2 → TxA2 → spontaneously converts to TxB2 → stimulates platelets

Front 13

What expresses Prostacyclin Synthase? Action?

Back 13

Endothelial cells express Prostacyclin Synthase, which converts PGG2 and PGH2 → PGI2 → inhibits platelets from sticking to each other

Front 14

What is necessary to prevent platelets from aggregating when there is no endothelial injury?

Back 14

Endothelial cells express Prostacyclin Synthase, which converts PGG2 and PGH2 → PGI2 → inhibits platelets from sticking to each other

Front 15

How do platelets mediate aggregation

Back 15

- Platelets express GPIIIa and GPIIb
- These receptors bind Fibrinogen
- Fibrinogen binds to other GPIIIa and GPIIb receptors on other platelets binding the two together leading to aggregation

Front 16

What are the types of platelet disorders?

Back 16

Quantitative:
- Decreased platelet count
- Prolonged bleeding time

Qualitative:
- Normal platelet count
- Prolonged bleeding time

(can have a mixture of both types of defects)

Front 17

What are the causes of defects of platelet adhesion (qualitative defect)?

Back 17

- Von Willebrand's Disease (cofactor abnormality)

- Bernard-Soulier Syndrome (platelet abnormality)

- Ehlers Danlos Syndrome (substrate abnormality)
- Scurvy (substrate abnormality)
- Pseudoxanthoma Elasticum (substrate abnormality)

Front 18

What are the causes of defects of platelet secretion (qualitative defect)?

Back 18

Prostaglandin defects:
- Phospholipase defect
- Cyclooxygenase defect (aspirin and NSAIDs)
- Thromboxane synthase defect

Storage pool defects (SPD):
- Alpha SPD
- Delta SPD
- Alpha-Delta SPD

Front 19

What are the causes of defects of platelet aggregation (qualitative defect)?

Back 19

- Glanzmann's Thrombasthenia (membrane changes)
- Uremia (abnormal milieu)
- Fibrin split productions (abnormal milieu)

Front 20

What are the causes of defects of platelets due to increased utilization (quantitative defect)?

Back 20

- Diffuse Intravascular Coagulation
- Thrombotic Thrombocytopenic Purpura
- Abnormal Heart Valves

Front 21

What are the causes of defects of platelets due to increased destruction (quantitative defect)?

Back 21

- Idiopathic Thrombocytopenic Purpura (more common)
- Lupus Erythematosus (Abs against platelets)
- Drugs: Quinidine, and many others (cause development of Abs against platelets)

Front 22

What are the two forms of Idiopathic Thrombocytopenic Purpura (ITP)?

Back 22

- Acute ITP
- Chronic ITP

Front 23

What are the signs of Acute vs Chronic ITP?

Back 23

- Acute ITP: prominent bleeding and purpura, no prior bleeding history
- Chronic ITP: bleeding less prominent, long history of easy bruising, indolent

Front 24

Who is typically affected by Acute vs Chronic ITP?

Back 24

- Acute: usually children (M:F ~1:1), frequently preceded by a viral syndrome
- Chronic: usually adults (M:F ~ 1:3)

Front 25

What are the characteristics of ITP antibodies?

Back 25

- Platelet specific
- Restricted heterogeneity (IgG3 - κ and λ light chains)
- Antigenic heterogeneity (GPIb, GPIIb, or GPIIIa)
- Site of production of Abs: spleen and/or BM

Front 26

What kind of antibodies are there in ITP?

Back 26

- IgG3
- κ and λ light chains

Front 27

What do ITP antibodies target?

Back 27

Usually target surface proteins on platelets: GPIb, GPIIb, or GPIIIa
(remember IgG!)

Front 28

How do you diagnose ITP?

Back 28

Diagnosis of exclusion
- Must be evidence of immune thrombocytolysis (thrombocytopenia, normal or increased megakaryocytes, anti-platelet antibody)
- Absence of other causes of thrombocytopenia (lupus erythematosus, diffuse intravascular coagulation, drugs, lymphoma)
- Absence of splenomegaly

Front 29

What is the evidence for immune thrombocytolysis to make the diagnosis of ITP?

Back 29

- Thrombocytopenia (low platelet count)
- Normal or increased megakaryocytes (if these were low, then it is a production problem rather than a destruction problem)
- Anti-platelet antibody

Front 30

What other causes of thrombocytopenia must you rule out to make the diagnosis of ITP?

Back 30

- Lupus Erythematosus
- Diffuse Intravascular Coagulation
- Drugs
- Lymphoma

Front 31

There must be an absence of what physical exam feature to make a diagnosis of ITP? Why?

Back 31

Absence of splenomegaly - if spleen is enlarged it could be the cause of the thrombocytopenia

Front 32

How do you treat ITP?

Back 32

- Corticosteroids and IVIG
- Splenectomy (if corticosteroids aren't working)
- Immunosuppressive agents

Front 33

How effective are corticosteroids for treating ITP? Effects?

Back 33

- 70% response with high relapse rate
- Decreases antigen processing and antibody production

Front 34

How effective is a splenectomy for treating ITP? Effects?

Back 34

- 50% response with low relapse rate
- Removes antibody source and site of sequestration
- Must give Pneumovax to children (because they will be at increased risk for infections)

Front 35

Case 1:
- 18 yo female presents for evaluation of red rash on her bilateral ankles
- Progressively increased over 3 days
- First notice after playing v-ball
- No fever, chills, lymphadenopathy, recent illness or meds
- Last menstrual period was 3 weeks ago w/ moderate bleeding (5 days, no clots)
- Exam: petechiae on palate, rash on bilateral legs extending to knee
- WBC normal, Hemoglobin normal, platelet count low (6000)
- PT, INR, aPTT, and fibrinogen all normal

What is the most appropriate diagnostic study?
a) Platelet function assay
b) Peripheral blood smear
c) von Willebrand’s activity test
d) Rheumatoid factor
e) Factor VIII activity

Back 35

Peripheral blood smear

When you are given a choice in hematology about what test to do, it is almost always peripheral blood smear.

We want to know what is driving this thrombocytopenic condition. Are there leukemia cell? Are there other problems with RBC fragmentation? Other suggestions of platelet system being activated?

Front 36

Case 1:
- 18 yo female presents for evaluation of red rash on her bilateral ankles
- Progressively increased over 3 days
- First notice after playing v-ball
- No fever, chills, lymphadenopathy, recent illness or meds
- Last menstrual period was 3 weeks ago w/ moderate bleeding (5 days, no clots)
- Exam: petechiae on palate, rash on bilateral legs extending to knee
- WBC normal, Hemoglobin normal, platelet count low (6000)
- PT, INR, aPTT, and fibrinogen all normal

What does our differential diagnosis include?

Back 36

- Idiopathic Thrombocytopenic Purpura (ITP)
- Lupus Erythematosus
- Diffuse Intravascular Coagulation (no other lab abnormalities)
- Drugs (not taking any)
- Lymphoma (rule out with peripheral blood smear)

Front 37

Case 1:
- 18 yo female presents for evaluation of red rash on her bilateral ankles
- Progressively increased over 3 days
- First notice after playing v-ball
- No fever, chills, lymphadenopathy, recent illness or meds
- Last menstrual period was 3 weeks ago w/ moderate bleeding (5 days, no clots)
- Exam: petechiae on palate, rash on bilateral legs extending to knee
- WBC normal, Hemoglobin normal, platelet count low (6000)
- PT, INR, aPTT, and fibrinogen all normal

Patient is diagnosed with ITP. How should she be treated?

Back 37

Treatment with Prednisone and IVIG
- Her platelet counts respond to normal levels and the petechiae resolves
- No further bleeding complications

Front 38

What are the characteristics of these platelets?

Back 38

- They are large relative to RBCs (about the same size)
- We can see these platelets have granules (taken up dye)

Front 39

Case 1:
- Girl diagnosed with ITP
- Does well for 10 years without bleeding complications
- Presents for evaluation of fatigue
- She is a runner, but reports decreased exercise tolerance and loss of pace
- Current meds: aspirin for ankle pain and ibuprofen for menstrual cramps
- Vegetarian but eats fish and eggs
- Increased menorrhagia over past 2 years
- Exam: conjunctival pallor, mild tachycardia (100bpm), late systolic murmur, multiple bruises on bilateral upper extremities
- Labs: WBC and platelet counts normal; hemoglobin LOW and MCV LOW; PT, INR, aPTT, and fibrinogen normal

What is the most likely cause of this patient’s anemia?
a) Acute blood loss
b) Iron deficiency anemia
c) Vitamin B12 deficiency
d) Hemolytic anemia
e) Beta thalassemia minor

Back 39

Iron deficiency anemia (vegetarian, menorrhagia, aspirin & NSAIDs)

Front 40

Case 1:
- Girl diagnosed with ITP
- Does well for 10 years without bleeding complications
- Presents for evaluation of fatigue
- She is a runner, but reports decreased exercise tolerance and loss of pace
- Current meds: aspirin for ankle pain and ibuprofen for menstrual cramps
- Vegetarian but eats fish and eggs
- Increased menorrhagia over past 2 years
- Exam: conjunctival pallor, mild tachycardia (100bpm), late systolic murmur, multiple bruises on bilateral upper extremities
- Labs: WBC and platelet counts normal; hemoglobin LOW and MCV LOW; PT, INR, aPTT, and fibrinogen normal

What would you do to confirm diagnosis of iron deficiency anemia?

Back 40

- Ferritin
- Iron (transferrin) saturation
- Total iron binding capacity
- Reticulocyte count

Front 41

What are the causes of microcytic anemias?

Back 41

- Iron deficiency
- Anemia of chronic disease (inflammation)
- Thalassemias
- Sideroblastic anemia

Front 42

What type of anemia:
- ↓ MCV
- ↑ RDW (RBC Distribution Width)
- ↓ Iron Sat%
- ↓↓ Ferritin
- ↓↓ BM Iron

Back 42

Iron Deficiency Anemia

Front 43

What type of anemia:
- ↓/Nl MCV
- Nl RDW (RBC Distribution Width)
- ↓/Nl Iron Sat%
- Nl/↑ Ferritin
- ↑ BM Iron

Back 43

Anemia of Chronic Disease (inflammation)

Front 44

What type of anemia:
- ↓ MCV
- Nl/↑ RDW (RBC Distribution Width)
- ↑ Iron Sat%
- ↑↑ Ferritin
- ↑↑ BM Iron

Back 44

Thalassemias

Front 45

What type of anemia:
- ↓ MCV
- ↑ RDW (RBC Distribution Width)
- Nl/↑ Iron Sat%
- ↑ Ferritin
- ↑ BM Iron

Back 45

Sideroblastic Anemia

Front 46

Case 1:
- Girl diagnosed with ITP, returns 10 years later w/ complaints of fatigue
- Labs: WBC and platelet counts normal; hemoglobin LOW and MCV LOW; PT, INR, aPTT, and fibrinogen normal
- Von Willebrand's antigen, activity, and multimers normal
- Factor VIII activity normal
- Thrombin time normal
- Platelet function assay: prolongation on collagen/epi cartridge (>300s, Nl <180s); normal on collagen/ADP cartridge

What is the mechanism of the patient’s platelet function defect?
a) impaired platelet adhesion to endothelial damage due to impaired von Willebrand's factor collagen binding
b) quantitative defect in the number of platelets available for coagulation
c) decreased thrombin generation due to suppression of clotting factors
d) decreased platelet aggregation due to reduced formation of thromboxane A2
e) development of a factor inhibitor (autoantibody) against factor VIII

Back 46

Decreased platelet aggregation due to reduced formation of thromboxane A2

This is happening because the patient is on aspirin

Front 47

What happens in a Platelet Function Assay?

Back 47

- Take tube that has blood in it
- Platelets exposed to agonists that cause blood to clot (eg, collagen/Epi, collagen/ADP)
- Not very specific
- Epi and ADP promotes clotting

Front 48

If a patient's platelet function assay shows prolongation on collagen/epi cartridge (>300s, Nl <180s) but a normal on time for the collagen/ADP cartridge, what is your differential? How do you determine which is right?

Back 48

- Drugs (check what drugs they are on)
- Von Willebrand Factor problem (run von Willebrand studies)
- ITP (diagnosis of exclusion)

Front 49

What are the effects of Aspirin on platelets?

Back 49

- Decreases platelet aggregation by inhibiting COX-1
- Results in decreased thromboxane formation
- Thromboxane regulates platelet aggregation through mediating glycoprotein IIb/IIIa

Front 50

What is the function of primary hemostasis? What happens if there is a problem with it?

Back 50

- Primary hemostasis → formation pf platelet plug
- Problems → mucocutaneous bleeding, including petechiae and mucosal bleeding (epistaxis, gingival bleeding, menorrhagia)

Front 51

What are the types of disorders that affect primary hemostasis?

Back 51

- Qualitative and quantitative platelet defects
- vW disease
- Disorders of endothelium

Front 52

What initiates the extrinsic clotting cascade?

Back 52

Initiated by things that are outside of the blood and endothelium = Tissue Factor

Front 53

What initiates the intrinsic clotting cascade?

Back 53

Things in the blood = Factor XII and PK

Front 54

What is the function of the extrinsic vs intrinsic clotting cascade?

Back 54

- Extrinsic cascade gets coagulation started
- Intrinsic cascade links to inflammatory system and helps keep clotting going

Front 55

What is the final result of the coagulation via the intrinsic or extrinsic pathway?

Back 55

Fibrin clot - which occurs in and among platelets, leading to stopped bleeding, and wound healing

Front 56

What happens in the extrinsic pathway?

Back 56

- Tissue Factor activates Factor VII → TF-VIIa
- TF-VIIa activates Factor X → Xa
- Xa activates Prothrombin (II) → IIa with help from V, and PI
- IIa activates Fibrinogen → Fibrin

Front 57

What factors are involved in the Extrinsic Pathway?

Back 57

TF, 7, 10, 2, Fibrin
- Tissue Factor
- Factor VII
- Factor X
- Factor II (Prothrombin) w/ help from Factor V and PI
- Fibrinogen

Front 58

What happens in the intrinsic pathway?

Back 58

- PK and HMWK activate XII → XIIa
- XIIa activates XI → XIa
- XIa activates IX → IXa
- IXa activates X → Xa (requires factor VIII, PI)
- Xa activates Prothrombin (II) → IIa (requires factor V, PI)
- IIa activates Fibrinogen → Fibrin

Front 59

What factors are involved in the Intrinsic Pathway?

Back 59

PK + 12, 11, 9, 10 (requires 8), 2 (requires 5), Fibrin

- PK + Factor XII
- Factor XI
- Factor IX
- Factor X (requires factor VIII)
- Factor II (requires factor V)
- Fibrinogen

Front 60

What is the role of Vitamin K in the clotting cascade?

Back 60

Helps convert glutamic acid to γ-carboxy-glutamic acid via Carboxylase

γ-carboxy group helps these factors to bind Ca2+ which is necessary for the conformational changes to help these factors be activated

Front 61

Which factors and other proteins require Vitamin K?

Back 61

- Factors II, VII, IX, X (2, 7, 9, 10)
- Proteins: PC, S, Osteopontin

Front 62

What does the Prothrombin Time (PT) test?

Back 62

Extrinsic coagulation
(VII)

Front 63

What does the Activated Partial Thromboplastin Time (aPTT) test?

Back 63

Intrinsic coagulation
(XII, XI, IX, VIII)

Front 64

What does the Thrombin Clotting Time (TCT) test assess?

Back 64

Ability of fibrinogen to convert to fibrin in final common pathway

Front 65

What can cause an isolated prolonged Activated Partial Thromboplastin Time (aPTT)?

Back 65

Helps assess the intrinsic pathway:
- High Molecular Weight Kininogen deficiency
- Prekallikrein deficiency
- F XII deficiency
- F XI deficiency
- F IX deficiency
- F VIII deficiency
- Passovoy Deficiency
- Lupus anticoagulant

Front 66

How can you determine if there are antibodies to factors causing a deficiency or if there is just a genetic deficiency of a factor?

Back 66

Mixing Studies for Inhibitor:
- Only do this test if there is an abnormal PTT or PT to identify it due to antibodies

Front 67

If you mix a hemophiliac's blood (deficiency of factor) with a normal patient's blood, what will the results be for the PTT or PT?

Back 67

The PTT or PT will be normal because there will be 50% of that factor, and the test only detects deficiency if <20% levels of the clotting factor

Front 68

If you mix a patient with antibody to a certain factor with a normal patient's blood, what will the results be for the PTT or PT?

Back 68

PTT or PT will still be low because the normal factor from the normal patient will be neutralized by the antibody

Front 69

What can cause an isolated prolonged PT?

Back 69

Factor VII deficiency

Front 70

What can cause a prolonged PT and aPTT?

Back 70

Parts of final common pathway
- Factor X deficiency
- Factor V deficiency
- Factor II deficiency
- Fibrinogen deficiency

Front 71

What can cause an isolated prolonged TCT?

Back 71

- Afibrinogenemia
- Hypofibrinogenemia
- Hyperfibrinogenemia
- Dysfibrinogenemia
- FDPs
- Immunoglobulins
- Heparin

Front 72

What can cause bleeding if the screening tests come back normal?

Back 72

- Mild factor deficiency
- Thrombocytopenia
- Thrombocytopathia
- Vascular abnormality (scurvy)
- Factor XIII deficiency
- Antiplasmin deficiency

Front 73

Case 2:
- 5 yo boy seen post-anesthesia with post-operative bleeding
- He has been bleeding for 3 hrs after tonsils and adenoidectomy
- Spitting up blood without cough
- Intraoperatively, procedure was uneventful with mildly increased diffuse bleeding
- PMH: normal circumcision, recurrent sore throats treated w/ antibiotics, otherwise helathy
- Meds: clindamycin, ibuprofen, dexamethasone, fentanyl, propofol intraoperatively
- Normal family hx and social hx
- No history of bleeding or bruising symptoms
- Exam: no rashes or bruises
- Labs: all normal, except elevated PTT (41 sec)

What is the next most appropriate diagnostic step?
a) von Willebrand’s activity testing
b) Fibrinogen
c) Partial thromboplastintime 1:1 mixing study
d) Platelet function assay
e) D-dimer

Back 73

Partial thromboplastintime 1:1 mixing study

Is there a factor deficiency or is there an inhibitor / antibody that is prolonging the clotting time in the test tube? PTT mixing study is very fast so you should get the results very quickly

Front 74

Case 2:
- 5 yo boy seen post-anesthesia with post-operative bleeding
- He has been bleeding for 3 hrs after tonsils and adenoidectomy
- Spitting up blood without cough
- Intraoperatively, procedure was uneventful with mildly increased diffuse bleeding
- PMH: normal circumcision, recurrent sore throats treated w/ antibiotics, otherwise helathy
- Meds: clindamycin, ibuprofen, dexamethasone, fentanyl, propofol intraoperatively
- Normal family hx and social hx
- No history of bleeding or bruising symptoms
- Exam: no rashes or bruises
- Labs: all normal, except elevated PTT (41 sec)

What is the next appropriate management step?

Back 74

- Assessment of patient’s airway with intubation if required
- IV fluids
- Type and cross for blood transfusion
- Surgical hemostasis
- Further lab studies to continue making diagnosis

Front 75

Case 2:
- 5 yo boy seen post-anesthesia with post-operative bleeding
- He has been bleeding for 3 hrs after tonsils and adenoidectomy
- Spitting up blood without cough
- Intraoperatively, procedure was uneventful with mildly increased diffuse bleeding
- PMH: normal circumcision, recurrent sore throats treated w/ antibiotics, otherwise helathy
- Meds: clindamycin, ibuprofen, dexamethasone, fentanyl, propofol intraoperatively
- Normal family hx and social hx
- No history of bleeding or bruising symptoms
- Exam: no rashes or bruises
- Labs: all normal, except elevated PTT (41 sec)

- Patient returns to OR and hemostasis achieved w/ cautery, no evidence of trauma or lacerated vessels

- Labs: PTT still elevated and PTT 1:1 mix is corrected

What lab result would best explain the patient’s bleeding complications?
a) Lupus anticoagulant positive
b) ↓ factor VIII activity
c) Loss of highest weight von Willebrand’s multimers
d) ↓ fibrinogen
e) ↓ factor VII activity

Back 75

↓ factor VIII activity

There is a deficiency of one of the intrinsic pathway factors

Factor VII deficiency would be if it was a prolonged PT but normal PTT

Front 76

Case 2:
- 5 yo boy seen post-anesthesia with post-operative bleeding
- He has been bleeding for 3 hrs after tonsils and adenoidectomy
- Spitting up blood without cough
- Intraoperatively, procedure was uneventful with mildly increased diffuse bleeding
- PMH: normal circumcision, recurrent sore throats treated w/ antibiotics, otherwise helathy
- Meds: clindamycin, ibuprofen, dexamethasone, fentanyl, propofol intraoperatively
- Normal family hx and social hx
- No history of bleeding or bruising symptoms
- Exam: no rashes or bruises

* Labs: PTT still elevated and PTT 1:1 mix is corrected
* Factor VIII activity ↓ (13%), Factor IX nl (88%), Factor XI nl (125%), Factor XII nl (105%)

What is the appropriate diagnosis?

Back 76

Mild Hemophilia A

Front 77

What is a Hemophilia?

Back 77

Inherited bleeding disorder in which there is a deficiency or lack of Factor VIII (hemophilia A) or Factor IX (hemophilia B)

Front 78

Which factors are deficient in Hemophilia A and B?

Back 78

- Hemophilia A: deficient Factor VIII
- Hemophilia B: deficient Factor IX

Front 79

How do you get hemophilia?

Back 79

- 70% of cases are inherited (X-linked recessive)
- Typically expressed in males but carried in females
- Severity consistent between family members

- 30% of cases are new mutations

Front 80

What are the degrees of Hemophilia severity?

Back 80

- Mild hemophilia: 6-50%
- Moderate hemophilia: 1-5%
- Severe hemophilia: <1%

Front 81

What is the pattern of bleeding most commonly identified in hemophilia?

Back 81

- Ooozing - can’t stabilize the fibrin clot
- Late re-bleeding
- Articular bleeds (joints, soft tissues) - more common in defects of secondary hemostasis

Front 82

How should a patient with Hemophilia be treated?

Back 82

Treated with recombinant factor VIII (hemophilia A) or factor IX (hemophilia B)

Front 83

In a hemophilic patient who is given the recombinant factor they are missing, what could cause the factor activity to go down leading to bleeding?

Back 83

Development of an inhibitor (antibody) against that factor (this is the most serious complication of factor replacement therapy)

Front 84

How should you treat a patient with an inhibitor / antibody to a factor?

Back 84

- Polyclonal high affinity IgG Ab that neutralize the procoagulant function of fVIII or fIX
- Factor replacement therapy becomes ineffective unless antibody is removed