Normal Hemostasis

Slide 1 · Normal Hemostasis

Platelet adhesion and activation • fibrin reinforcement • endothelial regulation

Mechanisms and clinicopathologic correlations

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning goals

Describe the four overlapping phases after vascular injury.

Explain platelet adhesion, activation, recruitment and aggregation.

Link thrombin and fibrin deposition to plug stabilization.

Identify how intact endothelium limits and resolves clotting.

Vascular injury

Transient vasoconstriction

Platelet plug

Thrombin → fibrin

Stabilization / resolution

Slide 3 · Hemostasis is localized clot formation

Hemostasis limits blood loss at the site of vascular injury.

Platelets, clotting factors and the vessel wall act as an integrated system.

The intended product is a stable local plug—not generalized coagulation.

Platelets

Adhesion → aggregation

Coagulation

Thrombin → fibrin

Endothelium

Switch + localization

Localized, stable hemostatic plug

Slide 4 · Three participants perform different tasks

Platelets provide immediate adhesion, a cellular plug and a catalytic surface.

Coagulation proteins generate thrombin and polymerized fibrin.

Endothelium determines whether clotting proceeds, remains localized or resolves.

Platelets

Adhesion → aggregation

Coagulation

Thrombin → fibrin

Endothelium

Switch + localization

Localized, stable hemostatic plug

Slide 5 · Intact endothelium separates blood from matrix

Circulating platelets ordinarily do not contact subendothelial collagen or vWF.

An uninterrupted endothelial barrier also shields blood from vessel-wall tissue factor.

Barrier loss is a powerful spatial cue for hemostasis.

Lumen / flowing blood

Subendothelial collagen + vWF

Continuous barrier

Slide 6 · A vascular breach changes local exposure

Injury uncovers extracellular matrix and subendothelial vWF.

Platelet-adhesive surfaces and tissue factor become accessible at the same lesion.

The injury site coordinates primary and secondary hemostasis.

Lumen / flowing blood

Subendothelial collagen + vWF

Exposed matrix

Slide 7 · Four processes overlap after injury

Transient vasoconstriction reduces local blood flow.

Platelets assemble the primary plug while tissue factor drives thrombin production.

Fibrin stabilizes the plug; Counterregulation later promotes resolution.

Vascular injury

Transient vasoconstriction

Platelet plug

Thrombin → fibrin

Stabilization / resolution

Slide 8 · Vasoconstriction is the immediate response

Arterioles constrict within moments after vessel injury.

The reduced lumen temporarily limits blood delivery to the lesion.

This buys time for platelet and coagulation-factor responses.

Narrowed

Lumen

Neural reflex + endothelin

Slide 9 · Neural reflexes and endothelin narrow vessels

Reflex neurogenic mechanisms contribute to early vasoconstriction.

Locally released endothelial endothelin can augment the response.

The effect is short-lived and cannot independently provide lasting hemostasis.

Narrowed

Lumen

Neural reflex + endothelin

Slide 10 · Why vasoconstriction alone is insufficient

Vessel narrowing is transient, so flow can return before tissue repair.

Without platelet and fibrin plug formation, bleeding can resume.

Hemostasis therefore requires rapid cellular and enzymatic reinforcement.

Platelet bridges

Fibrin polymerization

Platelet contraction

Clot dissolution + repair

Slide 11 · Primary and secondary hemostasis are coupled

Primary: Adhesion and aggregation form a platelet-rich initial seal.

Secondary: Thrombin converts fibrinogen to fibrin, reinforcing that seal.

They are overlapping biochemical programs, not isolated compartments.

Primary

Platelets adhere, activate and bridge through fibrinogen.

Secondary

Thrombin generation polymerizes fibrin around the platelet mass.

Slide 12 · Platelets arise from megakaryocytes

Platelets are anucleate circulating cell fragments released from marrow megakaryocytes.

Their resting shape is a small disk; Activation rapidly changes their form.

Specialized receptors, granules and cytoskeleton determine function.

GpIb–vWF

GpVI / GpIa-IIa

GpIIb/IIIa

Membrane + granules

Slide 13 · Platelets serve two hemostatic roles

An adhesive/aggregating surface rapidly seals small vascular defects.

Activated platelets concentrate coagulation reactions on membrane phospholipids.

Thus, platelet dysfunction impairs both the initial plug and its fibrin reinforcement.

Platelets

Adhesion → aggregation

Coagulation

Thrombin → fibrin

Endothelium

Switch + localization

Localized, stable hemostatic plug

Slide 14 · Each platelet receptor has a distinct ligand

GpIb binds von Willebrand factor, permitting adhesion to exposed matrix.

GpVI and GpIa/IIa recognize collagen.

Activated GpIIb/IIIa binds fibrinogen, supporting platelet-to-platelet linkage.

GpIb–vWF

GpVI / GpIa-IIa

GpIIb/IIIa

Membrane + granules

Slide 15 · α-granules carry adhesive and repair proteins

Contents include fibrinogen, vWF and coagulation factors V and XI.

Also contain fibronectin, platelet factor 4, PDGF and TGF-β.

Their release supplies local proteins relevant to coagulation and wound repair.

α-granules

VWF · fibrinogen · factors V/XI

PF4 · PDGF · TGF-β

Dense granules

ADP · ATP · Ca²⁺

Serotonin · epinephrine

Slide 16 · Dense granules supply rapid soluble signals

Dense granules contain ADP, ATP and ionized calcium.

Serotonin and epinephrine are also present.

Released ADP recruits and activates additional platelets near the injury.

α-granules

VWF · fibrinogen · factors V/XI

PF4 · PDGF · TGF-β

Dense granules

ADP · ATP · Ca²⁺

Serotonin · epinephrine

Slide 17 · Granule cargo links aggregation and repair

Dense-granule ADP supports self-amplifying recruitment.

α-granule proteins supply adhesive/coagulation components and repair signals.

Granule secretion is part of platelet activation, not a late bystander event.

Dense-granule emphasis

Rapid small-molecule release: ADP and Ca²⁺.

α-granule emphasis

Adhesive proteins, coagulation components and growth factors.

Slide 18 · Adhesion begins at exposed matrix

Endothelial disruption brings circulating platelets into contact with the ECM.

Subendothelial collagen and vWF provide adhesion substrates.

This initial tethering initiates activation and plug development.

Collagen / subendothelial ECM

GpIb

VWF

Platelet ↔ vWF ↔ collagen

Slide 19 · VWF bridges platelet GpIb to collagen

VWF associates with exposed subendothelial collagen.

Its platelet-binding interaction with GpIb captures platelets at the lesion.

The bridging molecule and its platelet receptor are both essential to normal adhesion.

Collagen / subendothelial ECM

GpIb

VWF

Platelet ↔ vWF ↔ collagen

Slide 20 · VWF is especially important under high shear

High-shear blood flow favors the vWF-dependent adhesion mechanism.

VWF simultaneously interacts with collagen and platelets, serving as a tether.

This explains why defects can particularly compromise rapid platelet capture.

VWF-mediated capture at exposed collagen

Slide 21 · Platelets also engage collagen directly

GpVI and the GpIa/IIa complex are platelet collagen receptors.

Direct collagen interaction complements GpIb–vWF tethering.

Several receptor–ligand pairs cooperate rather than representing one exclusive route.

Collagen / subendothelial ECM

GpIb

VWF

Platelet ↔ vWF ↔ collagen

Slide 22 · Adhesion and aggregation use different bridges

Adhesion links a platelet to the exposed vessel wall.

Aggregation links platelets to each other.

VWF/GpIb primarily mediates wall tethering; Fibrinogen/GpIIb-IIIa mediates interplatelet bridges.

Adhesion

Platelet GpIb ↔ vWF ↔ matrix collagen.

Aggregation

Platelet GpIIb/IIIa ↔ fibrinogen ↔ adjacent platelet.

Slide 23 · Von Willebrand disease illustrates failed tethering

Genetic deficiency of vWF impairs platelet–matrix adhesion.

The resulting defect is in primary hemostatic plug formation.

The disorder illustrates the functional importance of a plasma–matrix bridging protein.

Collagen / subendothelial ECM

GpIb

VWF

Platelet ↔ vWF ↔ collagen

Slide 24 · Bernard–Soulier syndrome localizes to GpIb

GpIb is the platelet receptor for von Willebrand factor.

Inherited deficiency of GpIb disrupts the same adhesion interface from the platelet side.

Distinct molecular lesions can impair the same hemostatic step.

VWF defect

Bridge protein unavailable or dysfunctional.

GpIb defect

Platelet receptor for that bridge is deficient.

Slide 25 · Adherent platelets undergo activation

Adhesion rapidly initiates shape change and granule secretion.

Membrane receptor conformations and lipid distribution also change.

These linked transformations prepare platelets for recruitment and coagulation.

Resting disc

Activated projection-rich surface

Adhesion / thrombin / ADP

Slide 26 · Activation converts disks into spiky cells

Resting platelets are relatively smooth, rounded disks.

Activated platelets develop projecting processes and markedly greater surface area.

Shape remodeling increases their interaction with the local plug and matrix.

Resting disc

Activated projection-rich surface

Adhesion / thrombin / ADP

Slide 27 · Platelet cytoskeleton drives mechanical change

The contractile cytoskeleton underlies shape remodeling.

Later contraction pulls aggregated elements into a more consolidated plug.

Platelet function is therefore both biochemical and mechanical.

Resting disc

Activated projection-rich surface

Adhesion / thrombin / ADP

Slide 28 · Activated GpIIb/IIIa binds fibrinogen

Activation alters the conformation of GpIIb/IIIa.

The altered receptor has increased affinity for circulating fibrinogen.

This transition enables fibrinogen to link neighboring platelets.

Inactive GpIIb/IIIa

Low-affinity configuration for fibrinogen.

Activated GpIIb/IIIa

High-affinity fibrinogen binding enables bridging.

Slide 29 · Phosphatidylserine exposes a catalytic surface

Activation translocates negatively charged phospholipids, especially PS, outward.

These membrane lipids concentrate calcium-dependent coagulation-factor complexes.

The activated platelet thus accelerates local thrombin production.

Activated platelet phospholipid surface: Exposed PS

Enzyme

Cofactor

Substrate

Ca²⁺ supports membrane assembly

Slide 30 · Calcium supports assembly of coagulation complexes

Several coagulation reactions occur on a negatively charged lipid surface.

Calcium helps organize membrane-bound proteins within those complexes.

Platelet-derived calcium and surface exposure couple primary to secondary hemostasis.

Activated platelet phospholipid surface: Exposed PS

Enzyme

Cofactor

Substrate

Ca²⁺ supports membrane assembly

Slide 31 · ADP is a platelet recruitment signal

ADP is released from dense granules of activated platelets.

Nearby platelets respond and themselves release additional granule contents.

This amplifying cycle expands the primary plug locally.

ADP + TxA₂ recruit neighboring platelets

Slide 32 · ADP stimulates P2Y₁ and P2Y₁₂ receptors

Platelets carry both P2Y₁ and P2Y₁₂ G-protein–coupled receptors.

ADP binding contributes to platelet activation and recruitment.

P2Y₁₂ antagonism interrupts an established amplification pathway.

ADP / P2Y receptors

TxA₂

Thrombin / PAR-1

Slide 33 · Recruitment turns a few adherent cells into a plug

Initially, only a small number of platelets contact the vessel-wall lesion.

ADP secretion promotes successive rounds of platelet activation.

Platelet mass accumulates rapidly through nearby recruitment and aggregation.

ADP + TxA₂ recruit neighboring platelets

Slide 34 · Thrombin activates platelets through PAR-1

Thrombin cleaves and activates the platelet PAR-1 receptor.

PAR-1 is a protease-activated G-protein–coupled receptor.

This establishes a direct feedback link from coagulation to platelet activation.

ADP / P2Y receptors

TxA₂

Thrombin / PAR-1

Slide 35 · Activated platelets produce thromboxane A₂

Platelet activation induces synthesis of thromboxane A₂ (TxA₂).

TxA₂ strongly promotes platelet aggregation and recruitment.

Its local signaling cooperates with ADP and thrombin.

ADP + TxA₂ recruit neighboring platelets

Slide 36 · Aspirin interrupts TxA₂-dependent aggregation

Aspirin inhibits platelet cyclooxygenase required for TxA₂ synthesis.

Reduced TxA₂ signaling attenuates platelet aggregation.

The mild bleeding defect illustrates pharmacologic inhibition of primary hemostasis.

Without aspirin

Cyclooxygenase activity permits TxA₂ synthesis.

With aspirin

Cyclooxygenase inhibition decreases TxA₂-dependent recruitment.

Slide 37 · Antiplatelet therapies target amplification nodes

P2Y₁₂ antagonists interrupt the ADP recruitment pathway.

PAR-1 antagonism interferes with thrombin-dependent platelet activation.

These targets act downstream of initial matrix exposure.

ADP / P2Y receptors

TxA₂

Thrombin / PAR-1

Slide 38 · Three signals reinforce platelet activation

ADP secretion recruits additional responsive platelets.

TxA₂ synthesis sustains platelet activation and aggregation.

Thrombin generation provides a simultaneous coagulation-to-platelet feedback loop.

ADP / P2Y receptors

TxA₂

Thrombin / PAR-1

Slide 39 · Fibrinogen forms bridges between platelets

Activated GpIIb/IIIa binds fibrinogen with high affinity.

A fibrinogen molecule can bridge receptors on adjacent platelets.

Multiple bridges establish the primary platelet aggregate.

Fibrinogen bridges

GpIIb/IIIa binding on neighboring platelets

Slide 40 · The initial platelet aggregate is reversible

Early aggregation may disperse before the plug matures.

Concomitant thrombin generation amplifies platelet activation.

Stable platelet contraction and fibrin deposition help make the plug definitive.

Platelet bridges

Fibrin polymerization

Platelet contraction

Clot dissolution + repair

Slide 41 · Thrombin stabilizes platelet aggregation

Thrombin induces additional platelet aggregation through PAR-1.

It also promotes irreversible platelet contraction.

Its role extends beyond fibrin formation to direct modification of the platelet plug.

Aggregated platelets

Primary platelet plug

Slide 42 · Glanzmann thrombasthenia demonstrates bridge failure

Inherited GpIIb/IIIa deficiency impairs fibrinogen-mediated aggregation.

Platelets may encounter the wound but cannot efficiently connect to one another.

The defect is mechanistically distinct from impaired vWF/GpIb adhesion.

Fibrinogen bridges

GpIIb/IIIa binding on neighboring platelets

Slide 43 · Platelet contraction consolidates the aggregate

The activated platelet cytoskeleton pulls the aggregated cell mass together.

Contraction makes the plug more compact and stable.

In parallel, fibrin deposition strengthens the architecture.

Aggregated platelets

Fibrin mesh

Slide 44 · Other blood cells can become trapped in plugs

Entrapped red cells and leukocytes are found within hemostatic plugs.

Activated platelet P-selectin supports leukocyte adhesion.

These cellular elements accompany the platelet–fibrin scaffold rather than defining its initiation.

Aggregated platelets

Fibrin mesh

Slide 45 · Exposed tissue factor initiates secondary hemostasis

Tissue factor is a membrane-bound vessel-wall procoagulant glycoprotein.

Smooth muscle cells and fibroblasts normally express TF beneath the endothelium.

Injury exposes TF to circulating blood, initiating local coagulation.

Vascular injury

TF exposed

TF + VIIa

Local initiation

Thrombin

Fibrin generation

Slide 46 · Tissue factor and factor VII launch thrombin generation

TF binds and activates factor VII at the injured site.

A cascade of proteolytic factor activations culminates in thrombin.

Tissue factor is the major in-vivo trigger; Details of factor networks belong to the adjacent cascade topic.

Vascular injury

TF exposed

TF + VIIa

Local initiation

Thrombin

Fibrin generation

Slide 47 · Activated platelet surfaces accelerate clotting

Coagulation steps assemble enzyme, substrate and cofactor on platelet phospholipids.

Calcium supports efficient assembly of these membrane-localized complexes.

Clotting reactions consequently intensify where platelets have been activated.

Activated platelet phospholipid surface: Exposed PS

Enzyme

Cofactor

Substrate

Ca²⁺ supports membrane assembly

Slide 48 · Thrombin converts fibrinogen into fibrin

Thrombin proteolytically cleaves soluble plasma fibrinogen.

The fibrin monomers polymerize into an insoluble fibrillar network.

Fibrin physically cements the aggregated platelet plug.

Soluble fibrinogen

Thrombin

Fibrin monomers

Insoluble polymerized network

Slide 49 · Factor XIIIa cross-links polymerized fibrin

Thrombin activates factor XIII in the coagulation pathway.

Factor XIIIa establishes covalent cross-links within the fibrin network.

Cross-linking strengthens the fibrin component of the hemostatic plug.

Factor XIIIa establishes covalent cross-links

Slide 50 · Thrombin couples fibrin formation and platelet activity

One thrombin output is fibrinogen cleavage and stabilization of fibrin.

Another is platelet activation through PAR-1.

Amplification of coagulation factors further sustains the local response.

Coagulation output

Fibrin polymerization and factor XIII activation.

Platelet output

PAR-1 signaling, aggregation and contraction.

Slide 51 · The definitive plug is platelet–fibrin composite

Platelets seal the breach rapidly through adhesion and aggregation.

Fibrin polymers create a reinforcing mesh around the platelet aggregate.

A stable secondary plug resists renewed bleeding during tissue repair.

Aggregated platelets

Fibrin mesh

Slide 52 · Clot contraction and fibrin create mechanical stability

Contractile platelets draw the aggregate into a compact mass.

An insoluble, cross-linked fibrin mesh reinforces that mass.

The clot is a temporary protective structure while the vessel heals.

Platelet bridges

Fibrin polymerization

Platelet contraction

Clot dissolution + repair

Slide 53 · Endothelium functions as a hemostatic switch

Uninjured endothelium actively prevents platelet activation and coagulation.

Injury or activation shifts the local surface toward a procoagulant phenotype.

This spatial contrast helps localize the plug to the injured region.

Intact endothelium

PGI₂ · NO · ADP degradation

Thrombomodulin · EPCR

Antithrombin activation · TFPI · t-PA

Injured / activated

Matrix and tissue factor exposed

Platelet recruitment and coagulation become favored

Slide 54 · Three endothelial factors restrain platelets

Prostacyclin (PGI₂) opposes platelet activation and aggregation.

Nitric oxide (NO) also inhibits platelet activity.

Endothelial ADPase removes extracellular ADP, interrupting recruitment.

Intact endothelial surface

PGI₂

NO

ADPase

Net effect: Platelet activation is restrained

Slide 55 · A continuous endothelial barrier is itself protective

Intact endothelial cells shield circulating platelets from subendothelial vWF and collagen.

They also prevent exposure of vessel-wall tissue factor to blood.

Physical separation works alongside active molecular anticoagulants.

Lumen / flowing blood

Subendothelial collagen + vWF

Continuous barrier

Slide 56 · Endothelium shifts thrombin toward anticoagulation

Thrombin binds endothelial thrombomodulin near intact vessel surfaces.

Endothelial protein C receptor (EPCR) presents protein C.

In this context, thrombin activates the protein C anticoagulant pathway.

Thrombin + thrombomodulin

EPCR + protein C

Activated protein C

APC + protein S inhibit Va and VIIIa

Slide 57 · Activated protein C and protein S inhibit Va and VIIIa

Protein C is converted to an active protease in the endothelial complex.

Protein S supports its anticoagulant activity.

The protein C–protein S system inactivates procoagulant cofactors Va and VIIIa.

Thrombin + thrombomodulin

EPCR + protein C

Activated protein C

APC + protein S inhibit Va and VIIIa

Slide 58 · Heparin-like endothelial molecules support antithrombin

Surface heparin-like molecules enhance antithrombin activity.

Antithrombin inhibits thrombin and several activated clotting factors.

This restrains coagulation as blood flows away from the injured focus.

Heparin-like endothelial molecules

Antithrombin activation

Inhibits IIa, IXa, Xa, XIa, XIIa

Slide 59 · TFPI restricts tissue-factor pathway activity

Endothelial tissue factor pathway inhibitor (TFPI) inhibits TF–VIIa complex activity.

Protein S acts as a cofactor for TFPI-mediated inhibition.

TFPI complements protein C and antithrombin in limiting propagation.

TF–factor VIIa complex

TFPI + protein S

⊣

Limits local pathway propagation

Slide 60 · Clotting stays local through redundant safeguards

Activated platelet surfaces favor coagulation at the vessel-wall breach.

Blood flow dilutes activated proteins; Liver clearance further removes them.

Adjacent intact endothelium supplies inhibitors that restrict clot extension.

Prohemostatic

Matrix/vWF exposure

Platelet activation

TF → thrombin

Fibrin formation

Restraining

NO / PGI₂ / ADPase

Protein C / antithrombin / TFPI

T-PA → plasmin

Slide 61 · Coagulation also triggers clot-removal pathways

The fibrinolytic response begins in parallel with clot formation.

Endothelial tissue plasminogen activator (t-PA) converts plasminogen to plasmin.

Plasmin mediates enzymatic breakdown of the fibrin scaffold.

Endothelial t-PA

Plasminogen → plasmin

Fibrin cleavage

Clot breakdown

Slide 62 · Plasmin cleaves fibrin during resolution

Plasmin degrades polymerized fibrin and limits further polymerization.

This helps constrain clot size and later remove the temporary plug.

Fibrin-derived breakdown products reflect the substrate being degraded.

Endothelial t-PA

Plasminogen → plasmin

Fibrin cleavage

Clot breakdown

Slide 63 · Plasmin activity is also counterregulated

Circulating α₂-antiplasmin rapidly inhibits free plasmin.

Plasminogen activator inhibitors (PAI) limit activator activity.

These brakes help prevent indiscriminate dissolution away from the clot.

Generate plasmin

Endothelial t-PA activates plasminogen on fibrin.

Limit proteolysis

α₂-antiplasmin neutralizes free plasmin; PAI checks activation.

Slide 64 · Fibrin localization focuses t-PA activity

T-PA is most active when bound to fibrin.

Its localization concentrates plasmin generation near the clot substrate.

This feature supports targeted fibrinolysis rather than generalized proteolysis.

Endothelial t-PA

Plasminogen → plasmin

Fibrin cleavage

Clot breakdown

Slide 65 · Clot resorption is linked to vessel repair

The protective plug must persist long enough to prevent recurrent hemorrhage.

Fibrinolysis then dismantles its fibrin component.

Hemostasis therefore includes both construction and regulated removal.

Platelet bridges

Fibrin polymerization

Platelet contraction

Clot dissolution + repair

Slide 66 · Primary defects produce a characteristic bleeding pattern

Defects in platelet function or vWF often cause skin or mucosal bleeding.

Petechiae/purpura, epistaxis and heavy menstrual bleeding are examples.

Coagulation-factor defects more often produce deep soft-tissue or joint bleeding.

Primary hemostasis defect

Mucocutaneous bleeding

Petechiae or purpura

Epistaxis / menorrhagia

Coagulation-factor defect

Bleeding into soft tissues or joints

Hemarthrosis may occur

Slide 67 · Clinical reasoning: Identify the failed interface

A patient has recurrent mucosal bleeding after minor trauma.

One candidate mechanism is defective vWF–GpIb-dependent adhesion.

Another is impaired GpIIb/IIIa–fibrinogen aggregation; Which step distinguishes them?

Candidate A

Failure to tether circulating platelets to the vessel wall.

Candidate B

Failure to bridge platelets into a growing aggregate.

Slide 68 · Clinical reasoning: Distinct step, similar phenotype

VWF/GpIb defects interfere with platelet–matrix tethering.

GpIIb/IIIa defects interfere with platelet–platelet aggregation.

Both compromise formation of a satisfactory primary plug despite different receptors.

Platelet–wall bridge

VWF / GpIb / collagen: Adhesion.

Platelet–platelet bridge

Fibrinogen / activated GpIIb/IIIa: Aggregation.

Slide 69 · The hemostatic balance has two equally necessary sides

Injury exposes vWF, collagen and tissue factor to initiate clot formation.

Normal endothelium restrains platelet recruitment and procoagulant proteases.

Fibrinolysis resolves the plug after its protective function is served.

Prohemostatic

Matrix/vWF exposure

Platelet activation

TF → thrombin

Fibrin formation

Restraining

NO / PGI₂ / ADPase

Protein C / antithrombin / TFPI

T-PA → plasmin

Slide 70 · Mechanistic synthesis: a stable clot with defined borders

Vasoconstriction briefly limits blood delivery; platelet adhesion starts the seal.

ADP, TxA₂ and thrombin amplify aggregation; fibrin stabilizes the structure.

Endothelial anticoagulants and t-PA prevent unchecked persistence and propagation.

Vascular injury

Transient vasoconstriction

Platelet plug

Thrombin → fibrin

Stabilization / resolution