Primary haemostasis: platelet adhesion, activation and aggregation
Primary haemostasis is the platelet plug, built in three steps. Learn where each antiplatelet drug acts and why aspirin's effect outlasts the tablet.
Chapters (14)
Trace platelet adhesion (von Willebrand factor and glycoprotein Ib), activation and aggregation (glycoprotein IIb/IIIa and fibrinogen), and name the antiplatelet drugs that block them: two drug classes act on activation, one class on aggregation, none on adhesion.
The short version
- Primary haemostasis is the platelet plug, the first seal on a damaged vessel, built in three steps: adhesion, activation, aggregation.
- Adhesion needs von Willebrand factor and GpIb; activation releases ADP and thromboxane A₂; aggregation needs fibrinogen bridging GpIIb/IIIa.
- Aspirin blocks COX-1, clopidogrel blocks P2Y₁₂ and tirofiban blocks GpIIb/IIIa; none of these drugs acts on adhesion.
- A platelet has no nucleus, so an irreversible block lasts the life of the platelet: aspirin's effect fades over 7–10 days.
- A failed ristocetin response points to GpIb or von Willebrand factor; normal ristocetin with no aggregation points to GpIIb/IIIa.
Primary haemostasis and the platelet plug
A man takes a low-dose aspirin every morning, then stops. Days after his last tablet, his platelets are still impaired. How does a drug leave its mark for a week?
The answer lies in primary haemostasis: the platelet plug, the first seal on a damaged vessel. It has three steps (adhesion, activation and aggregation), and the antiplatelet drugs are grouped by the step they hit.[1][6]
Think of the three steps as a sequence. First the platelets stick to the injured wall, then they switch on and call for help, then they link to one another. Each step has its own receptors and its own signals, and each can fail on its own.[1]
A platelet is an anucleate fragment of a megakaryocyte, so it can barely make new enzyme. Recovery needs new platelets from the marrow.[1][2]
Step 1, platelet adhesion: collagen, von Willebrand factor and GpIb
Injury exposes subendothelial collagen and von Willebrand factor. Von Willebrand factor is the bridge: it binds collagen on one side and platelet glycoprotein Ib (GpIb) on the other.[1]
Adhesion is therefore the step that depends on von Willebrand factor and GpIb, and none of the antiplatelet drugs in this lesson targets it.[1]
Without GpIb, in Bernard-Soulier syndrome, platelets cannot stick, and ristocetin cannot agglutinate them. The platelets are large and the count is low, and aggregation is normal to all agonists except ristocetin.[3][4]
Step 2, platelet activation: shape change, ADP and thromboxane A₂
Adherent platelets change shape, put out pseudopods and release their granules. Dense granules release ADP, calcium and serotonin.[1]
Platelets also make thromboxane A₂ from arachidonic acid, using the enzyme cyclooxygenase-1 (COX-1). ADP and thromboxane A₂ recruit more platelets and prime them for the next step.[1][2]
Step 3, platelet aggregation: GpIIb/IIIa and fibrinogen
Activation changes the shape of GpIIb/IIIa, the platelet's fibrinogen receptor. Fibrinogen now bridges platelets, and the plug grows.[1][4]
If GpIIb/IIIa is missing, as in Glanzmann thrombasthenia, platelets can stick but cannot clump. The count is normal, aggregation fails with every agonist, and the ristocetin response is normal.[3][4]
| Bernard-Soulier syndrome | Glanzmann thrombasthenia | |
|---|---|---|
| Missing receptor | GpIb | GpIIb/IIIa |
| Step affected | Adhesion | Aggregation |
| Ristocetin response | Abnormal | Normal |
| Aggregation to other agonists | Normal | Absent with every agonist |
Antiplatelet drugs: which step each one blocks
Of the drugs in this lesson, two classes act on activation, one on aggregation, and none on adhesion.[2]
| Step | Drug | Target | Block |
|---|---|---|---|
| Adhesion | None | – | – |
| Activation | Aspirin | COX-1, so thromboxane A₂ falls | Irreversible (acetylation) |
| Activation | Clopidogrel, prasugrel | P2Y₁₂ ADP receptor | Irreversible |
| Activation | Ticagrelor | P2Y₁₂ ADP receptor | Reversible |
| Aggregation | Eptifibatide, tirofiban | GpIIb/IIIa, so fibrinogen cannot bridge | Receptor blockade |
The antibody abciximab did the same, but is no longer marketed.[2]
Why aspirin's effect outlasts the tablet: recovery after stopping
An irreversible block lasts the life of the platelet. Aspirin's effect fades over 7–10 days. Platelet function recovers in about 5–7 days after clopidogrel, and 3–5 days after ticagrelor.[2]
So the hook has a simple answer. Aspirin irreversibly blocks COX-1, and a platelet can barely make new enzyme, so recovery has to wait for new platelets from the marrow.[1][2]
- Aspirin: irreversible COX-1 block, recovery 7–10 days
- Clopidogrel: irreversible P2Y₁₂ block, recovery 5–7 days
- Ticagrelor: reversible P2Y₁₂ block, recovery 3–5 days
Using it: platelet bleeding and the ristocetin response
Bleeding from the nose and gums, a normal platelet count and a normal PT and aPTT point to a platelet function problem, with mucocutaneous bleeding rather than joint bleeds.[3][5]
A platelet problem is a different pattern from a clotting-factor problem, which is why the screening result comes first.[5]
Then use ristocetin. A failed response points to GpIb or von Willebrand factor. Normal ristocetin with no aggregation points to GpIIb/IIIa.[3][4]
Practice question
Original · USMLE styleA 9-year-old boy has had frequent nosebleeds and gum bleeding since infancy. His parents are first cousins. He has had no joint bleeding. Laboratory studies show:
| Platelet count | 262,000/uL |
|---|---|
| Prothrombin time | 12 seconds |
| Activated partial thromboplastin time | 29 seconds |
| Bleeding time | prolonged |
Common questions
What are the three steps of primary haemostasis?
Platelet adhesion, activation and aggregation. Adhesion needs von Willebrand factor and GpIb; activation releases ADP and thromboxane A₂; aggregation needs fibrinogen on GpIIb/IIIa.
Why does aspirin's effect last a week after stopping?
Aspirin irreversibly acetylates COX-1, and a platelet has no nucleus, so it can barely make new enzyme. The block lasts the life of the platelet, and its effect fades over 7–10 days.
How do Bernard-Soulier syndrome and Glanzmann thrombasthenia differ?
Bernard-Soulier is GpIb deficiency: adhesion fails and the ristocetin response is abnormal. Glanzmann is GpIIb/IIIa deficiency: aggregation fails with every agonist and the ristocetin response is normal.
Which antiplatelet drugs act on activation and which on aggregation?
Aspirin (COX-1) and the P2Y₁₂ blockers clopidogrel, prasugrel and ticagrelor act on activation. Eptifibatide and tirofiban block GpIIb/IIIa and act on aggregation. None acts on adhesion.
Transcript
Read the full narration, by chapter645 words
0:00Why does one aspirin leave its mark for a week?
A man takes a low-dose aspirin every morning, then stops. Days after his last tablet, his platelets are still impaired. How does a drug leave its mark for a week? Today: trace platelet adhesion, activation and aggregation, and the drugs that block them.
0:17Primary haemostasis: the platelet plug, and a platelet with no nucleus
Primary haemostasis is the platelet plug, the first seal on a damaged vessel. A platelet is an anucleate fragment of a megakaryocyte, so it can barely make new enzyme; recovery needs new platelets from the marrow. Three steps: adhesion, activation, aggregation.
0:36Step 1, adhesion: collagen, von Willebrand factor, GpIb
Step one, adhesion. Injury exposes subendothelial collagen and von Willebrand factor. Von Willebrand factor is the bridge: it binds collagen on one side and platelet glycoprotein Ib on the other. Without glycoprotein Ib, in Bernard-Soulier syndrome, platelets cannot stick, and ristocetin cannot agglutinate them.
1:00Step 2, activation: shape change, ADP, thromboxane A2
Step two, activation. Adherent platelets change shape, put out pseudopods and release their granules. Dense granules release ADP, calcium and serotonin. Platelets also make thromboxane A2 from arachidonic acid, using the enzyme cyclooxygenase one. ADP and thromboxane A2 recruit more platelets and prime them for the next step.
1:26Step 3, aggregation: GpIIb/IIIa and fibrinogen
Step three, aggregation. Activation changes the shape of glycoprotein IIb/IIIa, the platelet's fibrinogen receptor. Fibrinogen now bridges platelets, and the plug grows. If glycoprotein IIb/IIIa is missing,
1:40Glanzmann thrombasthenia
as in Glanzmann thrombasthenia, platelets can stick but never clump. The count is normal, aggregation fails with every agonist, and the ristocetin response is normal.
1:55The drugs: aspirin, clopidogrel, ticagrelor, eptifibatide, tirofiban
Now the drugs, grouped by the step they hit: two act on activation, one on aggregation, and none on adhesion. Aspirin irreversibly acetylates cyclooxygenase one, so thromboxane A2 falls. Clopidogrel and prasugrel irreversibly block the P2Y12 ADP receptor; ticagrelor blocks it reversibly. Eptifibatide and tirofiban block glycoprotein IIb/IIIa so fibrinogen cannot bridge. The antibody abciximab did the same, but is no longer marketed. That answers the hook.
2:31Recovery after stopping, and the answer to the hook
An irreversible block lasts the life of the platelet: aspirin's effect fades over 7 to 10 days. Platelet function recovers in about five to 7 days after clopidogrel, and three to five after ticagrelor.
2:48Using it: bleeding from nose and gums, normal PT and aPTT
Now use it. Bleeding from the nose and gums, a normal platelet count, a normal PT and PTT: a platelet problem, with mucocutaneous bleeding rather than joint bleeds.
3:02The ristocetin response
A failed ristocetin response points to glycoprotein one B or von Willebrand factor. Normal ristocetin with no aggregation points to glycoprotein IIb/IIIa. The rule: adhesion is von Willebrand factor
3:15The rule
and glycoprotein Ib; activation is ADP and thromboxane; aggregation is glycoprotein IIb/IIIa and fibrinogen. Your turn.
3:29Practice question
A 9-year-old boy has had nosebleeds and gum bleeding since infancy. His parents are first cousins, and he has had no joint bleeding. The platelet count is 262,000 per microlitre, PT 12 seconds, APTT 29 seconds, and the bleeding time is prolonged. Aggregation studies show no response to ADP, collagen or epinephrine, and a normal response to ristocetin. Which of the following is most likely deficient? A, glycoprotein Ib. B, glycoprotein IIb/IIIa. C, von Willebrand factor. D, coagulation factor eight. E, platelet cyclooxygenase one. Pause here and decide. A is out: glycoprotein Ib deficiency would
4:21Answer and explanation
spoil the ristocetin response, and his is normal. C is out: a von Willebrand defect would give an abnormal ristocetin response, with aggregation to ADP and collagen intact. D is out: factor eight deficiency prolongs the APTT and causes joint bleeds; his APTT is normal. E is out: losing cyclooxygenase one blunts aggregation, but absent aggregation to every agonist is the signature of glycoprotein IIb/ IIIa. So the answer is B. Mucocutaneous bleeding since infancy, consanguinity, a normal count, normal clotting tests, normal ristocetin and absent aggregation: Glanzmann thrombasthenia.
5:12Recap and next lesson
Three things to keep. One: adhesion needs von Willebrand factor and glycoprotein one B; activation releases ADP and thromboxane; aggregation needs fibrinogen on glycoprotein IIb/IIIa. Two: aspirin blocks cyclooxygenase one, clopidogrel blocks P2Y12, and tirofiban blocks glycoprotein IIb/IIIa. Three: platelets have no nucleus, so an irreversible block lasts for the platelet's life. Next, the coagulation cascade: PT versus PTT.
Sources
Numbers in the text, e.g. [1], point here- Overview of the coagulation system. Indian J Anaesth 2014. europepmc.org/article/PMC/PMC4260295
- Antiplatelet Therapy in Heart Disease. Rev Cardiovasc Med 2025. europepmc.org/article/PMC/PMC12230833
- Glanzmann thrombasthenia. Orphanet J Rare Dis 2006. europepmc.org/article/PMC/PMC1475837
- Glanzmann thrombasthenia: genetic basis and clinical correlates. Haematologica 2020. europepmc.org/article/PMC/PMC7109743
- The bleeding child, Part II. Eur J Pediatr 2012. europepmc.org/article/PMC/PMC3258398
- OpenStax. Anatomy and Physiology 2e, 18.5 Hemostasis. openstax.org/books/anatomy-and-physiology-2e/pages/18-5-hemostasis
The opening patient is a hypothetical teaching vignette. Recovery times are the typical figures from the table in reference 2 and vary by drug label and country; abciximab was withdrawn from the market.
The practice question is original and its patient is synthetic. Every fact is checked against the sources above in independent accuracy reviews. Always follow your local guidelines and your own laboratory’s ranges.
Image credits. Illustrations: Servier Medical Art (smart.servier.com), CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/), adapted (cropped, recoloured, outlined): capsule, vessel injury and platelet plug. NIAID NIH BioArt Source (bioart.niaid.nih.gov), public domain: von Willebrand factor (968), cut blood vessel (806), platelet (415), GPIIb and IIIa (840), fibrinogen (841), platelet aggregation (928). Nose icon: Health Icons (CC0). The platelets, receptors, drug diagrams, aggregation traces, lab slip, bars and all handwriting are drawn in code (original).
Corrections. None so far. Spotted an error? Email info@medservatory.com with the lesson code MS-S1-HEME-010.
For exam study only, not medical advice. Read the medical disclaimer.
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