CSP Exam Prep: Bleeding Disorders (Hemophilia & Von Willebrand Disease)

Comprehensive vocabulary flashcards covering the pathophysiology, clinical phenotypes, diagnostic criteria, dosing, factor replacement products, novel non-factor therapies, and gene therapies for bleeding disorders from the NASP 2025 CSP Exam Prep Course.

Hemophilia A (HA)

A congenital bleeding disorder characterized by a deficiency in clotting Factor VIII, accounting for $80\text{--}85\%$ of all hemophilia cases and occurring primarily in males ($97\%$ male).

Hemophilia B (HB)

A congenital bleeding disorder characterized by a deficiency in clotting Factor IX, accounting for $15\text{--}20\%$ of all hemophilia cases and occurring primarily in males ($95\%$ male).

Severe Hemophilia Phenotype

A clinical classification of hemophilia characterized by clotting factor levels of $< 1\,\text{IU/dL}$ ($< 1\%$ of normal), which accounts for approximately $60\%$ of hemophilia cases.

Moderate Hemophilia Phenotype

A clinical classification of hemophilia characterized by clotting factor levels of $1\text{--}5\,\text{IU/dL}$ ($1\text{--}5\%$ of normal), representing approximately $15\%$ of hemophilia cases.

Mild Hemophilia Phenotype

A clinical classification of hemophilia characterized by clotting factor levels of $5\text{--}40\,\text{IU/dL}$ ($< 40\%$ of normal), representing approximately $25\%$ of hemophilia cases.

Von Willebrand Factor (VWF)

A plasma glycoprotein essential for hemostasis that serves as a carrier protein for Factor VIII; a functional deficiency in this protein causes Von Willebrand Disease.

Type 1 Von Willebrand Disease

The most prevalent subtype of Von Willebrand Disease, accounting for $60\text{--}80\%$ of cases, in which patients typically experience mild or no bleeding symptoms.

Type 2 Von Willebrand Disease

A subtype of Von Willebrand Disease representing $15\text{--}30\%$ of cases, presenting clinically with mild-to-moderate bleeding episodes.

Type 3 Von Willebrand Disease

The rarest and most severe subtype of Von Willebrand Disease, accounting for $5\text{--}10\%$ of cases, characterized by severe bleeding issues that often require factor replacement therapy.

Inhibitor

An alloantibody directed against infused clotting factor concentrate (CFC) that neutralizes the replacement factor; occurs in approximately $1$ in $5$ Hemophilia A patients and $3$ in $100$ Hemophilia B patients, most commonly within the first $50$ exposure days.

Bethesda Assay

A validated, often Nijmegen-modified laboratory blood test used to detect and quantify clotting factor inhibitors, recommended annually or upon loss of efficacy; thresholds are typically $> 0.6\,\text{BU}$ for Factor VIII and $> 0.3\,\text{BU}$ for Factor IX.

Immune Tolerance Induction (ITI)

A specialized treatment regimen for hemophilia patients with inhibitors that involves the daily administration of high doses of clotting factor concentrate over an extended period to induce immune tolerance.

Hemarthrosis

Bleeding into a joint cavity, representing the most common type of bleed in hemophilia patients; characterized clinically by swelling, warmth, pain, and loss of motion or difficulty in joint use.

Compartment Syndrome

A surgical emergency defined as a critical pressure increase within a confined anatomical space that causes a decline in perfusion pressure to local tissues, leading to tissue ischemia.

Prophylactic Hemostatic Dosing

The regular, scheduled administration of hemostatic agents to prevent bleeding episodes and preserve joints, recommended by treatment guidelines to be initiated before age $3$ or as early as possible.

Factor VIII Replacement Dosing Formula

The standard pharmacokinetic calculation used to determine dosing for Factor VIII: $\text{Dose (IU)} = \text{body weight (kg)} \times \text{Desired Factor VIII Rise (IU/dL or \%)} \times 0.5\,\left(\frac{\text{IU/kg}}{\text{IU/dL}}\right)$.

Altuviiio

A recombinant extended half-life (EHL) Factor VIII product that utilizes Fc-VWF-XTEN fusion technology and provides weight-based dosing ($50\,\text{IU/kg}$ once weekly for prophylaxis) without requiring pharmacokinetic testing.

Emicizumab (Hemlibra)

A humanized bispecific monoclonal antibody targeting Factor IXa and Factor X that bridges them to mimic activated Factor VIII; approved for routine subcutaneous prophylaxis in Hemophilia A with or without inhibitors.

Concizumab-mtci (Alhemo)

A monoclonal antibody rebalancing agent that inhibits tissue factor pathway inhibitor (TFPI) to improve thrombin generation; approved for routine once-daily subcutaneous prophylaxis in patients age $12$ and older with Hemophilia A or B who have inhibitors.

Marstacimab-hncq (Hympavzi)

A monoclonal antibody rebalancing agent that targets tissue factor pathway inhibitor (TFPI) to improve thrombin generation; approved for routine weekly subcutaneous prophylaxis in patients age $12$ and older with Hemophilia A or B without inhibitors.

Fitusiran (Qfitlia)

A rebalancing agent administered subcutaneously every $2$ months that reduces antithrombin to elevate thrombin levels in patients age $12$ and older with Hemophilia A or B (with or without inhibitors); requires antithrombin activity monitoring to maintain a target of $15\text{--}35\%$.

Bypassing Agents

Hemostatic therapies containing activated clotting factors—specifically activated prothrombin complex concentrate (aPCC) and recombinant Factor VIIa (rFVIIa)—used to treat or prevent bleeding in hemophilia patients with inhibitors by promoting clot formation independently of Factor VIII or IX.

Etranacogene dezaparvovec-drlb (Hemgenix)

An adeno-associated virus (AAV) vector-based gene therapy administered as a single IV infusion at a dose of $2 \times 10^{13}\,\text{genome copies/kg}$ for adults with Hemophilia B on Factor IX prophylaxis or with a history of serious hemorrhage.

Valoctocogene roxaparvovec-rvox (Roctavian)

An AAV5 vector-based gene therapy given as a single IV infusion at a dose of $6 \times 10^{13}\,\text{vector genomes/kg}$ for adults with severe Hemophilia A without baseline anti-AAV5 antibodies; requires semen donation avoidance and pregnancy prevention for $6$ months post-infusion.

Fidanacogene elaparvovec-dzkt (Beqvez)

An AAVRh74var capsid vector-based gene therapy administered as a single IV infusion at $5 \times 10^{11}\,\text{vector genomes/kg}$ (dose-adjusted for $\text{BMI} > 30\,\text{kg/m}^2$) for adults with severe Hemophilia B lacking neutralizing antibodies to AAVRh74var.

Vonvendi

A recombinant Von Willebrand factor replacement product indicated for Von Willebrand Disease; contraindicated in patients with known hypersensitivity to the product, excipients, or hamster/mouse proteins.