122 Hemophilia A and Hemophilia B

Question 1

Mode of inheritance of hemophilia

Answer 1

Sex-linked/X-linked

Question 2

TRUE O FALSE

In patients with hemophilia, clot formation is delayed because of the decreased thrombin generation.

Answer 2

TRUE

In patients with hemophilia, clot formation is delayed because of the decreased thrombin generation.

Question 3

Hemophilia A results when mutations occur in the F8 gene located on the

Answer 3

Long arm of the X-chromosome (X-q28)

Question 4

TRUE OR FALSE

All the sons of affected hemophilic males are hemophiliacs.

Answer 4

FALSE

All the sons of affected hemophilic males are normal.

• All the daughters are obligatory carriers of the F8 defect.
• Sons of carriers have a 50% chance of being affected
• Daughters of carriers have a 50% chance of being carriers themselves.

Question 5

One of the most common mutations, accounting for 40% to 50% of severe hemophilia A patients, is

Answer 5

“Combined gene inversion and crossing over”

The “inversion–crossing over” mutations result in severe hemophilia, and approximately 20% of these patients are susceptible to developing antibody inhibitors that neutralize factor VIII coagulant function.

In many cases of hemophilia, there is no family history of the disease, and at least 30% of the cases of hemophilia are a result of spontaneous (de novo) mutations.

Question 6

Patients with mild hemophilia A have a ____% lifetime risk of developing inhibitors and usually are diagnosed at an older age when compared with patients with severe hemophilia A.

Answer 6

5% to 10%

Question 7

The main risk factors for the antibody formation

Answer 7

Intensity of exposure to factor VIII and the type of genetic mutation

Question 8

TRUE OR FALSE

Hemophilia A in females is extremely rare

Answer 8

TRUE

Hemophilia A in females is extremely rare

Hemophilia A may occur in females with X chromosomal abnormalities such as Turner syndrome, X chromosomal mosaicism, and other X chromosomal defects.

Usually these manifestations are mild, but they may be serious during surgical procedures or after significant trauma.

Question 9

PRENATAL DIAGNOSIS AND CARRIER DETECTION

The current standard for identifying carrier status is through

Answer 9

Direct gene sequencing

Question 10

PRENATAL DIAGNOSIS AND CARRIER DETECTION

Carriers who harbor the intron 22 inversion or intron 1 inversion can be identified using

Answer 10

Southern blot technique and polymerase chain reaction

If these mutations are found to be absent, sequencing of the complete coding region is performed.

Prenatal diagnosis of hemophilia now can be performed almost routinely.

Question 11

Factor VIII level

Severe

Answer 11

≤1% of normal
(≤0.01 U/mL)

1. Spontaneous hemorrhage from early infancy
2. Frequent spontaneous hemarthroses and
   other hemorrhages, requiring clotting factor replacement

Question 12

Factor VIII level

Moderate

Answer 12

1%–5% of normal
(0.01–0.05 U/mL)

1. Hemorrhage secondary to trauma or surgery
2. Occasional spontaneous hemarthroses

Question 13

Factor VIII level

Mild

Answer 13

6%–40% of normal
(0.06–0.40 U/mL)

1. Hemorrhage secondary to trauma or surgery
2. Rare spontaneous hemorrhage

Question 14

TRUE OR FALSE

Measurement of factor VIII level is not recommended in all carriers.

Answer 14

FALSE

Measurement of factor VIII level is recommended in all carriers.

Carriers with factor VIII levels significantly less than 50%, as a result of imbalanced X chromosome inactivation, may experience excessive bleeding after trauma (eg, childbirth or surgery).

Question 15

Hemarthroses

The joints most frequently involved, in decreasing order of frequency

Answer 15

Ankles, knees, elbows, shoulders, wrists, and hips

Question 16

Hemarthroses

Type of joints more likely to be involved

Answer 16

Hinge joints

Question 17

Hemarthroses

A major factor in the pathogenesis of hemophilic arthropathy

Answer 17

Iron deposits from residual blood

Question 18

Hemarthroses

Radiologic stages of hemophilic arthropathy

Answer 18

• Stage 0: normal joint
• Stage 1: fluid in the joint
• Stage 2: some osteoporosis and epiphyseal overgrowth; Epiphysis is wide
• Stage 3: subchondral bone cysts, Joint spaces exhibit irregularities
• Stage 4: prominent bone cysts with marked narrowing of joint space
• Stage 5: Obliteration of jointspace with epiphyseal overgrowth

Question 19

Defined by the occurrence of three or more spontaneous bleeds within a 6-month period.

Answer 19

Target joint

The joints most often involved are the ankles, knees, and elbows, which become chronically swollen.

Question 20

Hemorrhages occur into muscle in the following order of frequency:

Answer 20

Calf, thigh, buttocks, and forearm

pataas!

Question 21

Bleeding into fascia and muscle can result to a hemorrhage in a confined space compresses the arterial vasculature resulting in ischemic muscle injury

Answer 21

Compartment syndrome

Question 22

TRUE OR FALSE

Bleeding into the myocardium or erect penis is very unusual, perhaps explained by the high concentration of tissue factor in these tissues.

Answer 22

TRUE

Bleeding into the myocardium or erect penis is very unusual, perhaps explained by the high concentration of tissue factor in these tissues.

Question 23

Blood cysts that occur in soft tissues or bone

Answer 23

Pseudotumors

• Not associated with pain unless rapid growth or nerve compression occurs
• Tend to expand over several years and eventually become multiloculated

Question 24

Three types of pseudotumors

Answer 24

• Type 1- simple cyst that is confined by tendinous attachments within the fascial envelope of a muscle
• Type 2 - initially develops as a simple cyst in soft tissues such as a tendon, but it interferes with the vascular supply to the adjacent bone and periosteum, resulting in cyst formation and resorption of bone
• Type 3- is thought to result from subperiosteal bleeding that separates the periosteum from the bony cortex

Question 25

Pseudotumors often develop in what part of the body:

Answer 25

Lower half of the body Usually in the thigh, buttock, or pelvis ## Footnote But they can occur anywhere, including the temporal bone

Question 26

Imaging useful in the diagnosis of pseudotumor

Answer 26

CT or magnetic resonance imaging

Question 27

A reliable treatment of pseudotumor

Answer 27

Operative removal of the entire mass ## Footnote Because the pseudotumor likely will reform if it is not completely removed **Needle biopsies of pseudotumors should be avoided because of the risk of infection and hemorrhage.** **Embolization, percutaneous drainage, exeresis and filling of the dead cavity, and radiotherapy** of a pseudotumor have been reported and may be of value in **patients with inhibitors when surgery is not possible.**

Question 28

Most genitourinary bleeding/hematuria arises from the

Answer 28

Renal pelvis ## Footnote Usually from one kidney but occasionally from both

Question 29

# TRUE OR FALSE Antifibrinolytic agents, such as aminocaproic acid and tranexamic acid, should be avoided in individuals with hematuria because of the risk of forming clots and producing obstructing clots in the ureter and bladder

Answer 29

TRUE Antifibrinolytic agents, such as **aminocaproic acid and tranexamic acid, should be avoided** in individuals with hematuria because of the risk of **forming clots and producing obstructing clots** in the ureter and bladder

Question 30

Recommended factor level before performing a **lumbar puncture**

Answer 30

50% of normal

Question 31

The most frequent surgical procedure performed on patients with hemophilia

Answer 31

Dental extraction ## Footnote Appropriate **factor VIII replacement therapy, sometimes supplemented by antifibrinolytic agents,** can prevent intraoperative and postoperative hemorrhages Patients with hemophilia are treated with clotting factor **preoperatively and postoperatively** to prevent bleeding.

Question 32

# PT or aPTT Patients with severe hemophilia A have a prolonged

Answer 32

Activated partial thromboplastin time (aPTT) ## Footnote The prothrombin time (PT) and thrombin clotting time are normal.

Question 33

How to detect if the hemophilic plasma contains an **anti–factor VIII inhibitor antibody**

Answer 33

Mixing studies ## Footnote Hemophilic plasma is mixed with an equal volume of normal plasma The aPTT on a similar mixture is **prolonged**, but **incubation of the mixture for one or two hours at 37  C** is sometimes required to detect the prolongation.

Question 34

A definitive diagnosis of hemophilia A should be based on

Answer 34

Specific assay for factor VIII activity ## Footnote * Functional factor VIII coagulant activity is measured by **one-stage clotting assays** based on the aPTT. * **Chromogenic assays** for factor VIII activity also are used widely, but do not always agree with one-stage assays. * Although infrequently measured in practice, factor VIII antigen is measured by **immunologic assays**, which detect normal and most abnormal factor VIII molecules.

Question 35

If the **factor VIII antigen level is normal** but the **clotting activity is reduced**, the patient has a

Answer 35

Dysfunctional factor VIII molecule ## Footnote * Such patients have antigen-positive hemophilia, also referred to as **cross-reacting material (CRM)-positive**. * Patients in whom both the factor VIII antigen level and activity are nearly undetectable are said to be **CRM-negative**.

Question 36

# Differential Diagnosis Acts as a carrier of factor VIII in vivo

Answer 36

Von Willebrand factor (vWF) ## Footnote Although **factor VIII is synthesized normally** in patients with vWD, **the half-life of factor VIII is markedly shortened because the vWF “carrier” molecule is decreased or absent**.

Question 37

# Differential Diagnosis Other abnormalities in **vWD** that distinguish vWD from hemophilia A are **decreased vWF antigen level, and decreased vWF activity,** often measured using the

Answer 37

Ristocetin cofactor activity assay

Question 38

# Differential Diagnosis Type of vWD where **factor VIII levels may be very low** (<5% of normal), making it difficult to distinguish from classical hemophilia.

Answer 38

Type III vWD | AR to unlike majority VWD ## Footnote The lack of a sex-linked pattern of inheritance in the family will help in the differential diagnosis.

Question 39

# Differential Diagnosis Variant of vWD in which **vWF multimers are normal but plasma factor VIII levels are low**.

Answer 39

vWD-Normandy ## Footnote * **Decreased binding of factor VIII to vWF** --> shortening of the intravascular survival of factor VIII and thus reduced factor VIII activity * The Normandy variant of vWD should be **suspected in patients with mild hemophilia A who do not exhibit a sex-linked recessive inheritance pattern**

Question 40

# Differential Diagnosis TRUE OR FALSE Only deficiencies of factors VIII and IX cause chronic crippling hemarthroses, with a family history suggestive of an X-linked bleeding disorder.

Answer 40

TRUE **Only deficiencies of factors VIII and IX** cause chronic crippling hemarthroses, with a family history suggestive of an **X-linked** bleeding disorder. ## Footnote Hemophilia A must be distinguished from other hereditary blood clotting factor deficiencies that exhibit a prolonged aPTT, including **deficiencies of factors IX, XI, and XII, prekallikrein, and high-molecular-weight kininogen.**

Question 41

# Differential Diagnosis Factor deficiency that occurs in **males and females** and is a **milder** hemorrhagic disorder compared with severe hemophilia A or B.

Answer 41

Factor XI deficiency

Question 42

# Differential Diagnosis Factor deficiencies that are not associated with bleeding

Answer 42

Deficiencies of factor XII, prekallikrein, and high-molecular-weight kininogen

Question 43

# Differential Diagnosis Factor deficiencies that causes both the PT and aPTT to be moderately prolonged

Answer 43

Combined deficiency of factors V and VIII

Question 44

# TRUE OR FALSE Aspirin, nonsteroidal antiinflammatory drugs can be given safely to hemophilia patients

Answer 44

FALSE Avoidance of aspirin, nonsteroidal antiinflammatory drugs, and other **agents that interfere with platelet aggregation** ## Footnote **Acetaminophen or relatively specific cyclooxygenase (COX)-2 inhibitors such as celecoxib** have been recommended, but these drugs can be harmful when taken in excessive doses or for prolonged periods.

Question 45

# TRUE OR FALSE Prophylactic therapy is recommended in all severely affected patients, and it should be initiated before the onset of recurrent hemarthroses (primary prophylaxis) or as directed.

Answer 45

TRUE **Prophylactic therapy** is recommended in all **severely affected** patients, and it should be initiated **before the onset of recurrent hemarthroses** (primary prophylaxis) or as directed.

Question 46

Blood products that contain factor VIII

Answer 46

Fresh-frozen plasma and cryoprecipitate ## Footnote A disadvantage of plasma is that **large volumes** must be infused to achieve and maintain even minimal factor VIII levels. The highest factor VIII level that can be achieved with plasma is approximately **20%** of normal, which is not always attainable or sufficient for hemostasis.

Question 47

Cryoprecipitate, containing approximately how many units of Factor VIII

Answer 47

80 U of factor VIII in 10 mL of solution ## Footnote Individual bags of cryoprecipitate must be pooled, the factor VIII dose can only be estimated, and the product must be stored frozen

Question 48

Types of factor VIII concentrates

Answer 48

Plasma-derived factor VIII concentrate Recombinant factor VIII concentrate ## Footnote * standard half-life * extended half-life

Question 49

Half-life of factor VIII

Answer 49

8 to 12 hours

Question 50

**1U of factor VIII per kilogram of body weight** raises the circulating factor VIII level by approximately ________ U/mL

Answer 50

0.02 U/mL ## Footnote The site and severity of hemorrhage determine the frequency and dose of factor VIII to be infused.

Question 51

Dose of DDAVP

Answer 51

0.3 mcg per kilogram body weight | note effective sa severe! ## Footnote * Given **intravenously or subcutaneously** * Factor VIII levels increase **two- to threefold** above baseline in most, but not all, **mildly or moderately** affected patients with hemophilia A * *Patients with severe hemophilia A do not respond to DDAVP* * A **concentrated intranasal spray of DDAVP** also can be used (150 mcg in each nostril for adults and 150 mcg in one nostril for children weighing <50 kg).

Question 52

The peak response to DDAVP

Answer 52

**30–60 minutes** after dosing

Question 53

Who can use DDAVP

Answer 53

Patients with mild or moderate hemophilia A and in carriers whose baseline factor VIII levels are less than 0.5 U/mL, DDAVP may be used in lieu of blood products

Question 54

Side efffect of DDAVP

Answer 54

Hyponatremia ## Footnote DDAVP is a potent **antidiuretic**. Repeated administration of DDAVP results in a diminished response to the agent **(tachyphylaxis).**

Question 55

Dose of antifibrinolytic agents

Answer 55

Tranexamic acid: 1 g four times per day EACA: loading dose of 4 g to 5 g followed by 1 gram per hour by continuous IV infusion or 4 g every 4 to 6 hours orally for 2 to 8 days

Question 56

Antifibrinolytic therapy is contraindicated in the presence of

Answer 56

Hematuria ## Footnote Clots resistant to lysis may obstruct the ureters

Question 57

Fibrin glue/fibrin tissue adhesive contains

Answer 57

Fibrinogen, thrombin, and factor XIII

Question 58

Recommended factor VIII levels for secondary prophylaxis in target joints

Answer 58

>50% of normal for 6 to 8 weeks

Question 59

Considered as life-threatening hemorrhages

Answer 59

Retropharyngeal, retroperitoneal, and central nervous system bleeding, whether subdural, subarachnoid, or into the brain parenchyma ## Footnote * Retropharyngeal bleeding: factor VIII levels to **normal (1.0 U/mL)**. * For retroperitoneal hemorrhage, early treatment is required, and therapy should be continued for **7 to 10 days**; otherwise, bleeding may recur upon resumption of activity. * Even asymptomatic patients with a history of head trauma should receive at least **one dose of factor VIII as a prophylactic measure**, and this dose should be given **before diagnostic procedures such as a CT scan.**

Question 60

Treatment of a known **intracranial hemorrhage** should be maintained for a minimum of ______________, and the circulating factor VIII level should be kept above _______% throughout this period.

Answer 60

20 to 30 days 50%

Question 61

Replacement of Factor VIII for Surgical Procedures

Answer 61

Raised to **normal** levels before operation and maintained for **7 to 10 days or until healing is complete**. ## Footnote * Treatment can be started a few hours before surgery and continued intraoperatively using a continuous infusion or boluses every 8 to 12 hours. * *Postoperatively*, factor VIII levels should be monitored at least **one or two times per day** to ensure that adequate levels are maintained. * Because factor VIII may be “consumed” during surgery, factor VIII levels should be **monitored intraoperatively** and **doses of factor VIII higher than normal** may be required.

Question 62

Dosage of Prophylactic Therapy

Answer 62

Standard half-life factor VIII: **25 U to 40 U oper kilogram of body weight three times per week or every other day** Extended half-life factor VIII: **30 U to 50 U per kilogram twice weekly**

Question 63

**Bispecific**, **humanized IgG4 antibody** mimics the cofactor activity of activated factor VIII by **bridging factor IXa and factor X together** for the formation of the prothrombinase complex

Answer 63

Emicizumab | ONLY FOR PROPHYLAXIS NOT FOR BLEEDING!

Question 64

Initiation of **primary prophylaxis**

Answer 64

Before the age of 2 years or after the first joint bleed

Question 65

Initiation of **secondary prophylaxis**

Answer 65

After the onset of hemarthrosis ## Footnote Can be used for short periods of time or to manage target joints.

Question 66

# TRUE OR FALSE The risk of inhibitor development is higher in patients with large deletions and nonsense mutations when compared with small deletions/insertions and missense mutations.

Answer 66

TRUE The risk of inhibitor development is higher in patients with **large deletions and nonsense mutations** when compared with small deletions/insertions and missense mutations. ## Footnote Some studies have reported that vWF is immunomodulatory, so that **products containing vWF may be less likely to induce inhibitors** compared with highly purified products.

Question 67

The presence of inhibitors arise among:

Answer 67

Severely affected patients, after treatment at an early age ## Footnote Many have **gross gene rearrangements or the intron 22 inversion abnormality** of the factor VIII gene.

Question 68

Risk Factors for Development of Anti–Factor VIII Antibodies in Patients with Hemophilia A

Answer 68

* Disease severity: 80% of hemophilia A patients with inhibitors have **<1% factor VIII activity** * **Early exposure to factor VIII concentrates:** majority of high-titer inhibitors develop after <90 days of exposure to factor VIII * Genetic factors: 1. Family history of inhibitor development 2. Ethnic background: blacks > Hispanics > whites 3. Molecular defects: inversion and crossing over defect in intron 22, gene deletions, and nonsense point mutations resulting in patients without factor VIII antigen

Question 69

Factor VIII inhibitors are antibodies, most often of the immunoglobulin (Ig) ___ class and frequently restricted to the _____ subclass.

Answer 69

(Ig) G class IgG4 ## Footnote Antibodies against the **A2 and C domains of factor VIII** are most common.

Question 70

# TRUE OR FALSE Factor VIII inhibitors are time and temperature independent in vitro.

Answer 70

TRUE Factor VIII inhibitors are time and temperature dependent in vitro. ## Footnote The aPTT of a 1:1 mixture of plasma from a patient with an inhibitor and normal plasma is significantly **prolonged after incubation at 37  C for 1 to 2 hours**

Question 71

A common assay used for inhibitor detection and quantification

Answer 71

Bethesda assay ## Footnote The patient’s plasma is diluted such that, when the plasma is mixed with an equal volume of normal pooled human plasma and incubated for 2 hours at 37  C, the **factor VIII activity in the mixture is decreased by 50%**

Question 72

A modification of the Bethesda assay in which **buffer is used** instead of factor VIII–deficient plasma

Answer 72

Nijmegen assay

Question 73

**High responders** are defined as patients whose inhibitor titer is ## Footnote Approximately **60%** of patients who have inhibitors are **high responders.**

Answer 73

* Higher than 5 Bethesda units (BU) at baseline OR * Initial inhibitor titer is less than 5 BU but rises to greater than 5 BU after administration of factor VIII

Question 74

# High-Responder Patients Dose of Factor VIII if to be used

Answer 74

Loading dose of **10,000 U to 15,000 U** may be required, followed by up to **1000 U of factor VIII per hour**, depending on the factor VIII level ## Footnote When the **initial titer is low**, sufficient **factor VIII can be administered in high doses** to neutralize the inhibitor and attain adequate factor VIII levels for hemostasis. One can expect an **anamnestic response** approximately **five days** after administration of factor VIII.

Question 75

# High-Responder Patients Dosing of Recombinant factor VIIa

Answer 75

**90 mcg to 120 mcg per kilogram** of body weight or higher every **2 to 3 hours**

Question 76

# High-Responder Patients Dosing of Factor VIII inhibitor–bypassing activity (FEIBA)

Answer 76

**50 U to 100 U per kilogram** of body weight every **8 to 12 hours (not to exceed 200 U/kg/day)**

Question 77

# High-Responder Patients If factor VIII inhibitor–bypassing agent are not available which agents can be considered

Answer 77

* Nonactivated prothrombin complex concentrates OR * Plasma exchange with high-dose replacement factor VIII

Question 78

# High-Responder Patients Treatment * <5 BU, Minor Hemorrhage: * >5 BU, Minor Hemorrhage: * <5 BU, Major Hemorrhage: * >5 BU, Major Hemorrhage:

Answer 78

* <5 BU, Minor Hemorrhage: Recombinant factor VIIa; FEIBA * >5 BU, Minor Hemorrhage: Recombinant factor VIIa; FEIBA * <5 BU, Major Hemorrhage: **Factor VIII?**; recombinant factor VIIa; FEIBA * >5 BU, Major Hemorrhage: Recombinant factor VIIa; FEIBA; **plasma exchange**

Question 79

**Low-responder** patients are arbitrarily defined as patients

Answer 79

Inhibitor titer is **less than 5 BU** even after a challenge with factor VIII

Question 80

# Low-Responder Patients Treatment * Major bleeding episodes: * Minor bleeding episodes:

Answer 80

* Major bleeding episodes: high doses of human factor VIII, recombinant factor VIIa or FEIBA * Minor bleeding episodes: recombinant factor VIIa or FEIBA ## Footnote Some “low” responders may convert to high responders when they are challenged repeatedly with factor VIII

Question 81

Adverse event associated with co-administration of FEIBA and emicizumab

Answer 81

Thrombosis

Question 82

The definitive goal of inhibitor management

Answer 82

Removal of the antibody

Question 83

Options for Immune Tolerance

Answer 83

* Plasmapheresis * Administration of IV γ-globulin * Immune tolerance regimens ## Footnote The **Malmö protocol** uses nearly all of these approaches in combination, including extracorporeal adsorption of antibody to a Sepharose A column, administration of cyclophosphamide, daily administration of factor VIII, and IV γ-globulin.

Question 84

Immune Tolerance regimens more effective in patients with acquired hemophilia resulting from autoantibodies against factor VIII

Answer 84

Immunosuppressive drugs, like cyclosporine and rituximab | Cause inhibitors in hemophilia are ALLOANTIBODIES

Question 85

The basis of immune tolerance regimens

Answer 85

Administration of frequent (daily or thrice weekly) doses of factor VIII until the inhibitor titer is undetectable High-dose Regimen: **200 U/kg factor VIII per day** Low-dose Regimen: **50 U/kg factor VIII three times per week**

Question 86

Predictors of success of immune tolerance regimens

Answer 86

* Young age at detection of inhibitor * Inhibitor titer less than 10 BU before starting immune tolerance induction (ITI) * Peak titer less than 200 BU after starting ITI * Historical peak titer less than 200 BU * Age less than 5 years old between diagnosis and start of ITI and * Genotype (small deletions and insertions, and missense mutations)

Question 87

Virus that can be transmitted with treatment modalities for hemophilia

Answer 87

Hepatitis A, B and C HIV ## Footnote All available factor VIII concentrates, both plasma-derived and recombinant products, are considered safe and effective with almost no risk of transmitting currently known viral diseases. However, occasional exceptions have been observed. For example, *solvent-detergent treatment does not inactivate prions and viruses without lipid envelopes, including the hepatitis A virus and parvovirus.*

Question 88

More than 30% of factor IX mutations occur at

Answer 88

CpG dinucleotides

Question 89

Disorder is characterized by **very low levels of factor IX antigen and activity at birth and during early childhood** The factor IX levels gradually **rise to 60% of normal or greater after puberty**, possibly caused by the age-related stability element/agerelated increase element-mediated genetic mechanism.

Answer 89

Hemophilia B Leyden phenotype

Question 90

# TRUE OR FALSE The hemophilia B population as a whole seems to have fewer and less severe complications than severely affected hemophilia A patients

Answer 90

TRUE The hemophilia B population as a whole seems to have **fewer and less severe complications** than severely affected hemophilia A patients

Question 91

# TRUE OR FALSE The occurrence of factor IX inhibitor antibodies is more common in patients with hemophilia B than in patients with hemophilia A.

Answer 91

FALSE The occurrence of factor IX inhibitor antibodies is much **less common** in patients with hemophilia B than in patients with hemophilia A and is **very rare in nonsevere disease.**

Question 92

The difference of dosing of Factor IX than VIII

Answer 92

Intravascular recovery of factor IX is only approximately 50%, and the recovery is even lower with the recombinant product

Question 93

**1 U of factor IX per kilogram body weight** increases circulating factor IX by

Answer 93

1% of normal, or 0.01 U/mL | Di na dinidivide by 2 ## Footnote Factor IX half-life of **18 to 24 hours**

Question 94

The prophylactic dose of standard half-life factor IX

Answer 94

25 to 40 U/kg of body weight two times per week

Question 95

The prophylactic dose of extended half-life factor IX

Answer 95

50 to 100 U/kg every 7 to 14 days

Question 96

Percentage of patients with severe hemophilia B who develop specific inhibitor antibodies

Answer 96

3% ## Footnote Frequently restricted in immunoglobulin composition to the **IgG4 subclass and κ light chains**

Question 97

# TRUE OR FALSE In contrast to the inhibitors in hemophilia A patients, inhibitor antibodies against factor IX are not time and temperature dependent; thus, incubating the mixtures for 2 hours at 37  C usually is unnecessary.

Answer 97

TRUE In contrast to the inhibitors in hemophilia A patients, inhibitor antibodies against factor IX are **not time and temperature dependent**; thus, incubating the mixtures for 2 hours at 37  C usually is unnecessary.

Question 98

# TRUE OR FALSE Acute DVT can be treated with heparin for 3 months as long as the patient receives factor replacement therapy.

Answer 98

FALSE Acute DVT can be treated with heparin for 7 to 10 days as long as the patient receives factor replacement therapy. ## Footnote Thereafter, anticoagulation is not recommended.

Question 99

For anticoagulation with heparin or vitamin K antagonists, factor trough levels recommended must be above

Answer 99

0.25 U/L