A 66-year-old woman presents to the emergency department complaining of palpitations. She says that she has been experiencing palpitations and lightheadedness for the past 6 months, but before this morning the episodes usually resolved on their own. The patient's medical history is significant for a transient ischemia attack 2 months ago, hypertension, and diabetes. She takes aspirin, metformin, and lisinopril. She states her grandfather died of a stroke, and her mom has a "blood disorder." An electrocardiogram is obtained that shows an irregularly irregular rhythm with rapid ventricular response, consistent with atrial fibrillation. She is given intravenous metoprolol, which resolves her symptoms. In addition to starting a beta-blocker for long-term management, the patient meets criteria for anticoagulation. Both unfractionated heparin and warfarin are started. Five days later, the patient begins complaining of pain and swelling of her left lower extremity. A Doppler ultrasound reveals thrombosis in her left popliteal and tibial veins. A complete blood count is obtained that shows a decrease in platelet count from 245,000/mm^3 to 90,000/mm^3. Coagulation studies are shown below: Prothrombin time (PT): 15 seconds Partial thromboplastin time (PTT): 37 seconds Bleeding time: 14 minutes Which of the following is the most likely diagnosis?

Type II heparin-induced thrombocytopenia

Type I heparin-induced thrombocytopenia

Idiopathic thrombocytopenia purpura

A 3-year-old girl is brought to her pediatrician because of a nosebleed that will not stop. Her parents say that she started having a nosebleed about 1 hour prior to presentation. Since then they have not been able to stop the bleeding. Her past medical history is remarkable for asthma, and she has a cousin who has been diagnosed with hemophilia. Physical exam reveals diffuse petechiae and purpura. A panel of bleeding tests are obtained with the following results: Bleeding time: 11 minutes Prothrombin time: 14 seconds Partial thromboplastin time: 32 seconds Platelet count: 195,000/mm^3 Peripheral blood smear shows normal cell morphology. Which of the following characteristics is most likely true about this patient?

Mutation in glycoprotein IIb/IIIa

Production of anti platelet antibodies

Production of antibodies against ADAMTS13

Decreased levels of von Willebrand factor

Seven days after undergoing bilateral total knee arthroplasty, a 65-year-old man comes to the physician with a dark discoloration and blisters on his abdomen. Current medications include simvastatin, aspirin, and low molecular weight heparin. His vital signs are within normal limits. Examination of the skin shows multiple coalescing blisters with areas of necrosis around the umbilicus. Laboratory studies show a platelet count of 32,000/mm3. Which of the following is the most likely underlying cause of this patient's symptoms?

Antibody formation against heparin-PF4 complex

Antibody-platelet antigen complex formation

Deficiency in ADAMTS13 activity

Anti-desmoglein antibody formation

A previously healthy 40-year-old woman comes to the physician because of a 3-day history of fever, headaches, and fatigue. She also reports a persistent tingling sensation in her right hand and numbness in her right arm that started this morning. Physical examination shows pallor, mild scleral icterus, and petechiae on her forearms and legs. On mental status examination, she appears confused and is only oriented to person. Laboratory studies show: Hemoglobin 11.1 g/dL Platelet count 39,500/mm3 Bleeding time 9 minutes Prothrombin time 14 seconds Partial thromboplastin time 35 seconds Serum Creatinine 1.7 mg/dL Total bilirubin 2.1 mg/dL A peripheral blood smear shows fragmented erythrocytes. Which of the following is the most likely underlying cause of this patient's condition?

Antibodies against double-stranded DNA

Absence of platelet GpIIb/IIIa receptors

An 8-year-old boy is brought to the pediatric emergency department by his parents with a complaint of abdominal pain and diarrhea for the past week. He states that for the past two days, he has noticed blood in his stool. His parents note that they attended a neighbor’s barbecue last weekend, but otherwise have not eaten any new foods or changed their usual diet. The patient is admitted to the hospital unit for further work-up. The provider team finds that the patient’s blood is positive for Shiga-like toxin and notes the following lab values: creatinine of 4.2 mg/dL, platelet count of 50,000/mm^3, and hemoglobin of 6.0 g/dL. Which of the following additional lab findings would be consistent with the diagnosis?

Microthrombi within glomerular vessels on kidney biopsy

Blunting of villi on ileal biopsy

Crypt abscesses and ulcers on colonic biopsy

Foamy macrophages in intestinal lamina propria on duodenal biopsy

Sickling of red blood cells on peripheral blood smear

Platelet disorders — USMLE Lesson

Platelet Basics - The Sticky Situation

Genesis & Lifespan: From bone marrow megakaryocytes. Lifespan 8-10 days. Normal count: 150,000-450,000/μL.
Primary Hemostasis Steps:
- Adhesion: von Willebrand Factor (vWF) links subendothelial collagen to the platelet GpIb receptor.
- Activation: Shape change; release of ADP & TXA2 recruits more platelets.
- Aggregation: Fibrinogen cross-links platelets via GpIIb/IIIa receptors, forming the plug.

Platelet Adhesion and Aggregation

⭐ Bernard-Soulier syndrome (impaired GpIb) causes defective adhesion. Glanzmann thrombasthenia (impaired GpIIb/IIIa) causes defective aggregation.

Thrombocytopenia - The Great Platelet Drop

Definition: Platelet count < 150,000/μL. Bleeding risk ↑ significantly when < 20,000/μL.
Etiology Buckets:
- ↓ Production: Marrow failure (aplastic anemia, MDS), chemo, radiation, alcohol, viral (HIV, HCV).
- ↑ Destruction:
  - Immune: ITP, HIT, SLE, drug-induced.
  - Non-immune (MAHA): TTP, HUS, DIC, HELLP. Schistocytes on smear are key!
- Sequestration: Splenomegaly (e.g., from cirrhosis).
- Dilutional: Massive transfusions.

⭐ Spontaneous bleeding is uncommon unless the platelet count drops below 10,000-20,000/μL. Petechiae and ecchymoses are classic signs.

MAHAs - Shreds, Clots & Trouble

Pathophysiology: Microvascular endothelial damage leads to platelet-rich thrombi, shearing RBCs into schistocytes ("helmet cells"), causing intravascular hemolysis.

Peripheral blood smear: schistocytes and thrombocytopenia

Core Syndromes:
- TTP (Thrombotic Thrombocytopenic Purpura): ↓ADAMTS13 activity. Causes large vWF multimers → platelet trapping. Neurologic symptoms are prominent.
- HUS (Hemolytic Uremic Syndrome): Often follows E. coli O157:H7 infection (Shiga toxin). Predominantly acute kidney injury.
- DIC (Disseminated Intravascular Coagulation): Widespread clotting & fibrinolysis. ↑PT/PTT, ↑D-dimer, ↓Fibrinogen.

⭐ The classic TTP pentad (fever, anemia, thrombocytopenia, renal & neuro findings) is rare. Suspect TTP with unexplained MAHA and thrombocytopenia alone.

Qualitative Disorders - Flawed & Useless Platelets

Presentation: Normal platelet count, but ↑ Bleeding Time. Patients present with mucocutaneous bleeding (epistaxis, gingival bleeding, petechiae).

Platelet surface receptors and their ligands

Disorder	Defect	Platelet Size	Key Lab Finding
Bernard-Soulier	↓ GpIb	Large (Big)	No aggregation with Ristocetin
Glanzmann	↓ GpIIb/IIIa	Normal	No aggregation with ADP, Epi, Collagen
Aspirin/NSAIDs	Acquired	Normal	Impaired thromboxane A2 synthesis
Uremia	Acquired	Normal	Impaired adhesion & aggregation

📌 Mnemonic: Bernard-Soulier has Big Suckers (large platelets).

High‑Yield Points - ⚡ Biggest Takeaways

Immune Thrombocytopenia (ITP) presents with isolated thrombocytopenia from anti-GpIIb/IIIa antibodies.

Thrombotic Thrombocytopenic Purpura (TTP) results from ADAMTS13 deficiency, causing the classic FAT-RN pentad.

Hemolytic Uremic Syndrome (HUS) is a triad of MAHA, thrombocytopenia, and AKI, often post-E. coli O157:H7.

von Willebrand Disease, the most common inherited type, causes impaired platelet adhesion.

DIC consumes clotting factors, causing ↑ PT/PTT/D-dimer with ↓ fibrinogen and platelets.

Bernard-Soulier (GpIb defect) impairs adhesion; Glanzmann's (GpIIb/IIIa defect) impairs aggregation.

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