Patho: hemostasis & bleeding disorders

platelets:

• Produced in bone marrow: megakaryocytes

  • Thrombopoietin: produced by liver & kidneys - major regulator of platelet production

• Shapes in circualtion:

  • Inactive: floating in circulation - round, smooth —> float through blood vessels easily

  • Active: clotting factors - spiky, sticky —> adhere to one another and blood vessel walls

• Damaged, after activated and no longer needed → spleen: broken into components → some reuses, others discarded at waste 

• Circulation: level amount in the bloodstream 

  • Typically 75% in circulation and 25% stored in liver & spleen

    • Normal level: 150,000-400,000 (abbreviated 15 – 40)

    • Low level: thrombocytopenia (below 15) → high risk for bleeding/inability to achieve hemostasis 

hemostasis: definition & balance

• Stop of bleeding/prevention of blood loss after blood vessel injury while maintaining as much blood flow within the vessel as possible

  • Allow blood flow through, while repairing damaged wall

• Maintain balance: adequate response

  • Excessive response: overproduction of blood clotting factors, over-activation of platelets 

    • Blood clot overgrow (thrombosis): take up too much space in vessel → compromised blood flow

      • Thrombosis —> ischemia —> necrosis

  • Insufficient response: don't activate appropriately, not enough platelets/clotting factors

    • Loose blood: bleeding, hemorrhage

hemostasis: functioning body systems & essential factors - normal hemostasis

• Functioning body systems:  

  • Bone marrow: produce blood cells - hematopoiesis

    • Megakaryocytes: platelets - TPO

    • Stem cell differentiation: RBC - EPO

    • Stem cell differentiation: WBC - CSF

  • Liver: coagulation factors (proteins that help the blood to clot), excretes RBC waste (bilirubin) in bile

  • Kidney: make EPO & TPO —> stim blood cell production in bone marrow

  • Spleen/macrophages: break down into components —> recycle, waste (liver)

  • GI: absorb it K (diet)

  • Systems need to function: bone marrow, GI tract, liver, spleen, kidneys

• Essential elements: calcium, vit K

hemostasis: process overview

• Pathway: injury to blood vessel → vascular spasm (vasoconstriction) → platelet plug → coagulation —> fibrinolysis during vessel repair

  • Injury: chemical, physical - needle stick, inflammation, puncture

    • Endothelial cells: irritated/damaged

    • Smooth muscle activates: vasoconstriction (vascular spasm) —> minimize blood flow

    • Endothelial cells: release signal messengers and coagulation factors

      • Signals platelets in circulation: resting inactive form —> active form

        • Aggregate, activate (sticky), adhere to bv wall (plug)

    • Temporary platelet plug formation

    • Blood clot: fibrin mesh woven over platelet plug to make the clot structured

      • allows for healing

      • prevents blood loss

    • fibrinolysis: clot dissolved while the blood vessel repairs

hemostasis: blood vessel layers

• Tunica adventitia: connective tissue holds all together

• Tunica media: smooth muscle - vasospasm in injury

• Tunica intima: endothelial cell layer - 1 cell layer thick (easy to damage/irritate→clot)

  • Contains products that contribute to hemostasis/clot formation

hemostasis: elements - thrombogenic

• Thrombogenic: make clot when needed - elements

  • In vessel wall:

    • Exposed endothelium: trigger clot formation

    • Collagen: negative charge - attract platelets

    • Tissue factor (thromboplastin, factor 3): triggers platelet aggregation & extrinsic clotting pathway

  • In circulating elements:

    • Platelets: aggregate

    • Prothrombin (factor 2): precursor to thrombin (factor 2a) - converts fibrinogen —> fibrin

    • Fibrinogen (factor 1): precursor to fibrin (factor 1a)

    • von Willebrand Factor (vWF): protein activates platelet adhesion

    • Clotting factors:

hemostatic elements: antithrombogenic

• Antithrombogenic: remove clot when not needed - elements

  • In vessel wall:

    • Heparin: produced by endothelial cells - inhibits thrombin (factor 2a)

    • Tissue plasminogen factor (tPA-plasminogen activator): converts plasminogen —> plasmin

    • Thrombomodulin: binds thrombin, activate protein C

  • In circulating elements:

    • Antithrombin: blocks thrombin and factor 10

    • Plasminogen: inactive form of plasmin - dissolves fibrin

    • Protein C & S: inactivate factors 5 and 8

hemostasis: stages

• Primary: initial injury to endothelial cells - vasospasm + platelet plug

  • Damage to BV: exposure of collagen (deeper BV layers)

  • Smooth muscle activated: vasoconstriction to minimize blood loss

  • Signal messengers/coag factors: activate platelets

  • Formation of a platelet plug

• Secondary: structure for clot - coagulation factors → fibrin mesh over platelet plug

  • Activation of clotting factors by intrinsic/extrinsic pathways

    • Common pathway factor X —> Xa for formation of fibrin (insoluble strands)

  • Clot components: platelets and fibrin

• Final stage: clot retraction, tissue rebuilds - activation of plasmin to dissolve clot

  • Retraction: decrease fibrin mesh development, dissolve clot when no longer needed

hemostasis: primary hemostasis

• Damage to vessel wall

  • Smooth muscle contracts: vasoconstriction to minimize blood loss 

  • Endothelium releases: tissue factor (TF, factor 3) - triggers platelet activation

  • Collagen exposed: surface for platelet adhesion

• Formation of platelet plug

• Activation of hemostasis: vWF (adhesion)& TF (PLT aggregation) and

primary hemostasis: vWF

• Von Willebrand factor (vWF): platelet adhesion

  • Synthesized: by endothelial cells & megakaryocytes

    • Majority: circulated in plasma, stored in platelets, some stored in endothelium

  • Released when there is an injury to the blood vessel 

    • Role: join platelets together and promote production of Clotting Factor VIII

      • After vascular injury, vWF acts as a bridge between endothelial collagen and platelet surface receptors to promote platelet adhesion

  • Carried by platelets: active → vWF → more clotting - positive feedback loop

positive feedback loop: platelets & vWF

• PLT release vWF packets, packets cause more clotting and activity - trigger vasoconstriction and promote aggregation (PLT can activate self)

  • Transform to self adhere in the presence of VWF

    • Main function: form mechanical plugs at site of vascular injury

      • Platelet glycoprotein complex I (GP-Ib) is the principal receptor for vWF

  • Structure: platelets carry vWF in cells 

    • Active: release clotting factor packets → sticky

• Active platelets: active in the presence of exposed collagen and vWF - 3 steps

  • Adhesion: platelet sticks to vessel wall

  • Aggregation: platelets stick to other platelets

  • Degranulation products: constriction & coagulation

platelet degranulation products

• Serotonin & histamine: triggers immediate vasoconstriction, promotes degranulation

• Thromboxane: triggers vasoconstriction, promotes aggregation

• adenosine diphosphate: stimulates aggregation by causing their plasma membranes to be ruffled and sticky, promotes degranulation

• Glycoprotein receptors: promotes platelet adhesion via Fibrin network

• Platelet factors: PF 3 - stimulates Coagulation Cascades, PF 4 - Heparin Neutralizing Factor

hemostasis: primary hemostasis - tissue factor & activation

• Primary initiator of coagulation: extrinsic pathway

  • Stored in subendothelial tissue and fibroblasts 

    • Localized: predominantly in tunica media/adventitia in a smaller quantity as circulating TF on monocytes

    • Higher concentrations in vital organs (heart, brain, lungs, uterus, testis, placenta)

• Becomes active when exposed to blood via disruption of the vessel: activated by

  • Physical/mechanical injury: activation of vessel wall TF

    • EX: cut, needle, puncture

  • Functional injury: inflammation in endothelium activates circulating TF

    • Hypoxia: low oxygen levels

    • Sepsis: systemic infection, massive inflammation

    • Malignancy: abnormal trigger clot cascade - by intact endothelial

      • Blood cancer, irritability in the blood vessels 

hemostasis: secondary hemostasis

• Activation of Clotting factors (intrinsic and extrinsic pathway)

  • Activated by platelets and in plasma

• Common Pathway converts Thrombin to Fibrin

  • Coagulation cascade:

    • Intrinsic pathway

    • Extrinsic pathway

    • Common pathway

• Insoluble Fibrin clot forms

clotting factors

• Produced by liver: majority are circulating in inactive form

  • Activation enables them to participate in clotting cascade by binding calcium and other elements

  • May be Vit K dependent

• Nomenclature of coagulation proteins is complex 

  • Not discovered in order so, numerals are not indicative of actual sequence

  • The first 4 of the 12 originally identified factors are often referred to by their common names, i.e., fibrinogen, prothrombin, tissue factor (TF), and calcium

    • Some factors have more than one name

      • VI no longer exists

coagulation cascade: vitamin K & pathways

• Driven by various clotting factors secreted primarily by the liver, platelets, and endothelium

  • The liver requires fat-soluble vitamins K to produce many of these (need functional GI)

    • Consumed in the diet: nutritional sources

    • Synthesized by the bacteria residing in the large intestine (antibiotics throw off)

• Cascade has two initial pathways that converge to create fibrin network to complete the secondary hemostasis process 

  • Intrinsic pathway: initiated by exposed collagen (platelet activation) 

  • Extrinsic pathway: initiated by release/activation of TF (damaged cells)

  • Common pathway: two pathways unite to create thrombin enzyme that converts fibrinogen into insoluble fibrin polymers that become part of the clot

hemostasis: final stage - clot retraction & fibrinolysis

• Antithrombogenic factors

  • Vessel wall: heparin, tissue plasminogen factor (tPA), thrombomodulin 

  • Circulating element: antithrombin, plasminogen, protein C & S

• Factors for clot dissolution: several factors release plasminogen activators during clotting cascade (XII, XIV, and thrombin)

  • Triggered by high concentration of thrombin

  • These cleave plasminogen to form plasmin

• Plasmin digests fibrinogen and fibrin and inactivates factors V and VIII

  • Fibrin split products result from the dissolution of the fibrin clot

fibrinolysis: clot dissolution

• Plasminogen releases: high thrombin levels 

• Plasmin activates: digests fibrin & inactivates V & VII

• Clot dissolves: fibrin degradation products

clinical evaluation: history

• Family history: inherited - hemophilia, von Willebrand disease

• Systemic disease: renal, liver, cancer, SLE, infection, aplastic anemia

• Prescription: NSAID (aspirin), anticoagulants, antibiotics, chemotherapeutics

  • NSAID: inhibit platelet aggregation 

  • Chemotherapy: suppress bone marrow activity - low plt, wbc, rbc

• Diet: ETOH alcohol overuse (liver damage), deficiency (B12, folate, vit K)

clinical evaluation: physical exam

• skin

• mucous membranes

• labs

physical exam finding: pallor & jaundice

• pallor: pale

  • Inadequate perfusion

  • Not enough blood in circulation

• jaundice: yellow of skin

  • liver diseased

  • bile build up in the body

physical exam finding: petechiae & ecchimosis

• petechiae: small red dots

  • microhemorrhage in capillary bed

• ecchymosis: bruise

physical exam finding: hematoma

• bump elevated

• collection of blood

physical exam finding: hematochezia & melena

• Hematochezia: bright red blood in stool

  • close to exit

• Melena: black tarry stool

  • deeper

  • more time

  • slow bleed 

physical exam finding: hematuria & hematemesis

• Hematuria: blood in urine 

• Hematemesis: bright red blood in vomit

physical exam finding: epistaxis & hematoptysis

• Epistaxis: nose bleed

• Hemoptysis: blood coming up in cough

  • Source of bleeding in lungs

physical exam finding: hemarthrosis & menorrhagia

• Hemarthrosis: bleeding into joints

• Hemarthrosis: bleeding into joints

sources of bleeding: characteristics

• Arteries: spurting blood, pulsating flow, bright red color 

• Veins: steady, slow flow, dark red color 

• Capillaries: slow, even flow

labs to assess blood

• CBC

• PLT

• PT/INR

• PTT

• Fibrinogen

• FDP

• D-dimer

labs: CBC

• CBC: complete blood count

  • Count whats in circulation

  • Identify anemia/infection

    • RBC, Hct, Hgb, WBC

labs: PLT

• PLT: number of platelets

  • 15-40 or 150,000-400,000

  • less than 15: thrombocytopenic - bleeding risk

labs: PT/INR

• prothrombin time - extrinsic pathway

  • PT: 10-14s - time it takes for blood to clot (initiated by TF)

    • Extrinsic, vit k def, hemorrhagic disease newborn, liver disease, DIC, anticoag therapy, all factors except VII and XII

    • warfarin

• international normalized ratio - extrinsic pathway

  • INR: 1.0 (therapeutic prolonged PT elevation: INR >2.0-2.5)

labs: PTT

• Partial thromboplastin time: intrinsic pathway (function of CF 8,9,11,12)

  • 33-45 (therapeutic prolonged PTT: 45-70 - heparin)

    • Heparin slows this process down

labs: fibrinogen

• Common pathway: both sides of cascade working, common pathway

  • 200-400mg/dL

    • decreases in liver disease, DIC

labs: FDP

• Fbrin degradation product: fibrinolysis (break down blood clot)

  • <3 ug/mL - byproducts from breakdown of fibrin clot

    • increase DIC, hypoxia, leukemia, thromboembolic disorders

labs: D-dimer

• Fibrinolysis: diagnose with clotting problem

  • <200ng/ml - want a low number

    • Increased DVT, PE, DIC

issues related to bleeding

• thrombosis: athlerosclerosis, AF, AAA (abdominal aortic aneurysm), hypercoagulable disorders

• bleeding disorders: vascular purpura, thrombocytopenia, thrombocytosis, hemophilia, vWD, vit k deficicency, DIC, liver disease

bleeding disorders: acquired v inherited

• Acquired: disorder develops secondary to tissue/organ injury or systemic disease

  • EX: thrombocytopenia, DIC,

• Inherited: disorder has genetic etiology

  • EX: Hemophilia, von willebrand disease

• Either: these conditions may be due to an acquired disease or injury (i.e. viral infection, Rx, malnutrition) or may be due to a genetic mutation (i.e. autoimmune hepatitis, metabolic dz)

  • EX: liver disease, vit K deficiency 

bleeding disorder: thrombocytopenia - def, type, cause, labs, treatment

• Inadequate platelet production: lack of/low functional platelets in circulation

  • type: dilutional/relative - low PLT relative to total circulating volume/other substances in circulation

    • Cause: pregnancy, excess IV fluids, blood transfusions

• Causes:

  • Bone marrow suppression: #1 cause

    • Rx: NSAIDs, chemo-suppress bone marrow

  • Hyperactive platelet destruction: viral pathogens (Ebola-hemorrhage)

    • Hyperactive spleen: pull PLT from circulation to break them down

  • Excessive splenic pooling: malaria

• Lab values: low PLT count (< 15), other labs like PTT & PT/INR may be normal

• Treatment: identify & correct cause - DC rx, antimicrobials, splenectomy, 

  • Platelet transfusion: centrifuge to separate 

    • NEVER give WBC, plasma (coag factors)

bleeding disorder: hemophilia - def, types, s/s, lab, treament

• Inherited: lack factors necessary for the intrinsic pathway of coagulation cascade —> deceased ability to form fibrin needed for insoluble clot

  • Types: may be mild or severe depending on degree of factor deficiency

    • Type A: lacking factor VIII (8)

    • Type B: lacking factor IX (9 - aka “Christmas Disease”)

• S/S: hemarthrosis of knees/ankles/elbows → joint deformity (hallmark condition)

• Lab values: elevated PTT (> 40) - left/intrinsic, other labs normal PLTs, PT/INR

• Treament:

  • Prophylactic factor VIII or IX replacement

  • Fresh frozen plasma (FFP): contains all clotting factors - active bleeding

  • Cryoprecipitate (Cryo): FFP prepared from plasma with specific factors- contains fibrinogen, von Willebrand factor, factor VIII

  • Tranexamic acid (TXA): antifibrinolytic drug = inhibits fibrinolysis - active bleeding, menorrhagia (nebulized version - hemoptysis/epistaxis) 

bleeding disorder: von Willebrand disease - def, impacts, lab, treament

• Lack of adequate vWF available: lack of adhesion

  • Factor VIII deficiency: platelet dysfunction - not become “sticky” without vWF

• Impacts: primary hemostasis (platelet plug formation) & intrinsic pathway of coagulation cascade

• Lab values: elevated PTT (>40), normal PT/INR, PLTs

• Treatment:

  • Desmopressin (DDAVP): trigger release vWF

    • Induces release of vWF from endothelial cells: if any 

    • Enhances procoagulant activity of platelets

  • Cryoprecipitate: FFP prepared from plasma with specific factors- concentrated amount of vWF

  • Tranexamic acid (TXA): antifibrinolytic drug = inhibits fibrinolysis - active bleeding, menorrhagia (nebulized version - hemoptysis/epistaxis) 

bleeding disorders: vit K deficiency- def, cause, source, lab, treatment

• Low vitamin K levels: most common in newborn babies (takes time to build resources, gut sterile)

  • Lipid soluble Vit K is needed for liver to synthesize several coagulation factors

    • Low levels lead to impairment of coagulation cascade

• Causes:

  • Malnutrition (lacking in diet)

  • Malabsorption (GI dysfunction)

  • Liver dysfunction (inability to process lipids)

  • Antibiotic use/overuse (destroys healthy intestinal flora)

• Sources of Vit K include

  • Diet: green leafy vegetables, liver, milk, cheese, butter, egg yolks

  • Normal intestinal flora synthesize a version of vit K: antibiotics

• Labs: elevated PT/INR (>14 / >2), normal PLTs, PTT

• Treatments: identify & tx cause

  • Vit K replacement (phytonadione, diet): injection

  • Fresh Frozen Plasma (FFP): coag factors

bleeding disorder: liver disease- def, cause, labs, treatment

• Importance: large number of clotting factors are produced in the liver

  • Dysfunction: clotting factor abnormalities

  • Secondary hemostasis is inhibited

• Causes:

  • Infection: Hep C virus - vets

  • ETOH overuse: alcoholic cirrhosis (scar tissue)

  • Non-alcoholic fatty liver disease (NAFLD) r/t obesity & diabetes

  • Toxins: death cap mushroom

  • Genetic disorders: hemochromatosis - excessive iron

• Labs: abnormal

  • Elevated PTT (>40)

  • Elevated PT/INR (>14 />2)

  • Decreased PLTs (<15)

• Treatment: identify & tx cause

  • Admin Vit K supplement

  • Transfuse FFP, PLTs, Cryo: replace missing coag factors

  • Tranexamic acid (TXA): antifibrinolytic drug = inhibits fibrinolysis - active bleeding, menorrhagia (nebulized version - hemoptysis/epistaxis) 

bleeding disorders: DIC - definiton, cause, labs, treatment

• DIC: acquired hemorrhagic syndrome - both abnormal clotting & bleeding from over-use of resources

  • Endothelial vessel inflamed: activate clotting cascade abnormally - use up resources

    • Initiated by tissue factor or thromboplastin

    • Widespread clotting in small peripheral vessels 

    • Over-consumption of platelets and clotting factors 

    • Injury: no resources left to deal with bleeding 

  • Causes include:

    • Damaged endothelium (burns/trauma/sepsis/retained placenta, peripartum)

    • Excessive release clotting factors (snake venom/cancers)

    • Excessive synthesis of clotting factors (blood transfusion reaction)

    • Stagnant blood flow (shock states)

  • Labs: constant monitoring of labs (q2hr) - critical care

    • Elevated PT/INR (>14 / >2)

    • Elevated PTT (>40)

    • Elevated FDP/FSP (>10)

    • Low PLTs (<15)

  • Treatment options: identify & tx cause - give 

    • Cryoprecipitate or transfuse FFP: prepared from plasma with specific factors- concentrated amount of vWF

    • PLTs: replacement coagulation factors

    • Anticoagulants: antithrombogenic drugs

      • Heparin

      • Protein C

bleeding disorders: nursing considerations - patient & family education

• no contact sports

• no tattoos

• soft bristle toothbrush

• electric shavers (no razor blades)

• gentle nose blowing

• keep nails short

• stool softeners/laxatives

• monitor stool & urine

• avoid NSAIDs

• contraceptives to prevent menorrhagic

bleeding disorders: nursing considerations - general

• Fall prevention

• No rectal temps

• Avoid IM injections

• Cluster blood test sampling 

• Advocate for central line

• Avoid prolonged use of constrictive items: restraints, tourniquets, TED hose, wrist bands

• Manual BP cuff: automatic may get too tight & cause ecchymosis

• Minimize risk for hemorrhagic stroke: elevate HOB, maintain normal BP, avoid bearing down

• Treatment prior to invasive procedures