HEMA Chapter 41 (Reading Assignment)

This set of flashcards reviews key concepts in platelet biology, disorders, and methods of evaluation and treatment.

• Identifies the cause of prolonged APTT

• Distinguishes weak lupus anticoagulant from factor deficiencies

What is the significance of specific tests like PTT-LA in patients with prolonged APTT?

They may vary based on phospholipid content and affect lupus anticoagulant detection.

What can sensitive variations of APTT reagents indicate?

At the start of Vitamin K Antagonist (VKA) therapy in patients with lupus anticoagulant.

When is chromogenic Factor X (FX) preferred over INR for monitoring patients?

They may develop an autoantibody against prothrombin, leading to severe bleeding and prolonged PT and APTT

What rare condition can occur in patients with strong lupus anticoagulant?

Adhesion, aggregation, and secretion during hemostatic processes.

What is the importance of platelet function in hemostasis?

Inherited disorders, acquired disorders, autoimmune processes, and drug interactions.

What abnormalities affect platelet counts and function?

von Willebrand factor (VWF)

A protein that mediates platelet adhesion and carries factor VIII in the blood.

Using manual platelet counts, peripheral blood films, and specialized platelet function tests.

How are platelet disorders commonly diagnosed?

GPIIb-IIIa and GPIb-IX-V

What are the key types of glycoproteins involved in platelet aggregation?

PS translocates to the outer membrane leaflet, essential for coagulation.

What changes occur in platelet phosphatidylserine (PS) during activation?

Signaling pathways trigger changes that expose fibrinogen binding sites.

How does platelet activation influence aggregation?

Stimulates platelet aggregation and vasoconstriction.

What is the function of thromboxane A2 (TXA2) in platelets?

Mediates responses to ADP, leading to increased intracellular Ca²⁺ and aggregation.

How do P2Y receptors influence platelet function?

It irreversibly inhibits cyclooxygenase, reducing TXA2 production.

What is the mechanism of action of aspirin on platelets?

Autosomal dominant but can also be autosomal recessive.

What is the inheritance pattern of von Willebrand Disease (VWD)?

It involves gain-of-function mutations in vWF leading to increased platelet binding and thrombocytopenia.

What distinguishes Type 2B von Willebrand disease?

Type 1 VWD involves decreased vWF levels while maintaining normal functionality.

What is the most common subtype of von Willebrand Disease (Type 1)?

By analyzing vWF levels, factor VIII levels, and performing aggregation studies using ristocetin.

How can bleeding risks be assessed in patients with suspected VWD?

von Willebrand factor (VWF)

What factor is essential for binding platelets in VWD?

They are critical for adequate platelet aggregation and adhesion.

What do large multi-mers of vWF indicate upon activation?

It causes accumulation of large vWF multimers, increasing thrombotic risk.

What physiological impact does ADAMTS13 deficiency have?

Myeloproliferative neoplasms and autoimmune disorders

What blood disorders can lead to increased platelet function variability?

Platelet-type is due to mutations in GP1BA, enhancing vWF binding, leading to impaired clearance.

What defines the difference between platelet-type and classical von Willebrand Disease?

Markedly impaired platelet aggregation due to defective GPIIb-IIIa complex.

What do patients with Glanzmann thrombasthenia present with?

Autoantibodies targeting platelet surface antigens leading to reduced platelet survival.

What is usually observed in patients with autoimmune-associated thrombocyto-penia?

Regulates secretion and aggregation during platelet activation

How does calcium mobilization affect platelets?

Activates platelets via protease-activated receptors (PAR)

How is thrombin involved in platelet activation?

They serve as molecular switches transmitting signals from activated receptors to effectors.

What role do G proteins play in platelet signaling?

They inhibit cyclooxygenase, impacting TXA2 synthesis and prolonging bleeding times.

How do aspirin and other NSAIDs affect platelet aggregation?

Platelet aggregation studies using light transmittance and various agonists.

What laboratory technique assesses platelet function?

Impaired dense granule secretion leading to blunted aggregation responses.

What abnormality is noted in patients with storage pool deficiency?

Low levels of ADAMTS13 activity and presence of large vWF multimers.

What is the diagnostic hallmark of Thrombotic Thrombocytopenic Purpura (TTP)?

Symptoms resemble inherited VWD, often with loss of high-molecular-weight vWF multimers.

What are the clinical features of acquired von Willebrand syndrome?

Increased platelet counts, dysfunction, and blood viscosity.

What factors contribute to thrombotic events in myeloproliferative neoplasms?

Shape change, granule secretion, and exposure of receptor binding sites.

What cellular changes occur in platelets during activation?

Genetic analysis and functional assays to evaluate platelet responses.

What methods establish the presence of inherited platelet function disorders?

It identifies genetic anomalies linked to platelet function deficits.

What is the importance of high-throughput sequencing in diagnosing platelet disorders?

Modulates platelet activity and hemostatic functions.

How does hormonal influence affect platelets?

Endothelial cells synthesize it, with further storage in platelets.

What is the main cellular source of von Willebrand factor?

It stimulates vWF release from endothelial cells, enhancing platelet function.

How does desmopressin (DDAVP) work in hemostasis?

Interactions among surface receptors, intracellular signaling pathways, and environmental cues.

What primarily regulates platelet activation?

Storage and secretion of ADP, calcium, and other mediators during aggregation.

What is the primary function of dense granules in platelets?

They help in quantifying platelet aggregation responses to specific agonists.

How are platelet function assays crucial in diagnosing VWD?

Acquired von Willebrand syndrome, characterized by similar bleeding tendencies.

What condition might mimic the symptoms of VWD in some patients?

ADAMTS13 activity levels: low in TTP, normal in aHUS.

What clinical measure helps differentiate between TTP and aHUS?

Based on platelet size, factor production defects, and genetic mutations.

How can inherited thrombocytopenia be characterized?

Wiskott-Aldrich syndrome

An X-linked disorder characterized by small platelets, eczema, and immunodeficiency.

• Glanzmann is due to GPIIb-IIIa defects,

• Bernard-Soulier results from GPIb-IX-V dysfunction.

What distinguishes Glanzmann thrombasthenia from Bernard-Soulier syndrome?

Caplacizumab, which inhibits the interaction of vWF with its platelet receptor.

What is a potential new therapeutic approach for TTP?

Thrombocytopenia and platelet dysfunction, as both can contribute to bleeding.

What are the two main troubleshooting factors when evaluating bleeding disorders?

They can predispose to bleeding disorders and acute myeloid leukemia.

What are the clinical implications of genetic mutations in RUNX1 related to platelets?

Through high throughput sequencing which uncovers novel genetic links.

How does the genetic basis of inherited platelet disorders evolve with research?

Complexities of overlapping symptoms, genetic factors, and environmental influences.

What are the challenges in diagnosing platelet pathologies?

Release of ADP and other factors amplifies platelet activation and aggregation.

How does the secretion of granule contents affect platelet response?

Mobilizes granule release and promotes aggregation.

What is the role of calcium in platelet activation?

Reactive thrombocytosis is secondary to bodily processes, while primary is due to bone marrow disorders.

What distinguishes reactive thrombocytosis from primary thrombocytosis?