02 - Anemias, Hemostasis, and the Anticogulated Patient

anemia

read the MCV first

• microcytic — MCV ≤ 80 fL

  • main causes → iron deficiency, thalassemia

  • mechanism → not enough Hb made

  • oral clue → atrophic glossitis, angular cheilitis

• normocytic — MCV = 80-100 fL

  • main causes → hemolysis (sickle cell, G6PD), apalastic anemia, acute blood loss, chronic disease

  • mechanism → cells destroyed, lost, or not made

  • oral clue → jaundice, pallor

• macrocytic — MCV > 100 fL

  • main causes → vitamin B12 deficiency, folate deficiency

  • mechanism → DNA synthesis fails; cells cannot normally divide

  • oral clue → beefy red, smooth, or sore tongue

• normal hemoglobin values:

  • women → 12 g/dL

  • men → 13 g/dL

  • severe anemia → <7 g/dL

iron deficiency anemia

most common anemia in the world (microcytic)

• causes —

  • women → menstruation, pregnancy

  • men and postmenopausal women → GI bleeding, including colon cancer, until proven otherwise

• lab findings —

  • low ferritin → single best test

  • high total iron-binding capacity (TIBC) → low transferrin saturation

• oral findings — pallor, atrophic glossitis, angular cheilitis

  • Plummer-Vinson syndrome → iron deficiency, dysphagia from an esophageal web, glossitis, higher risk of oral and pharyngeal squamous cell carcinoma

vitamin B12 and folate deficiency

causes macrocytic anemia due to impaired DNA synthesis, resulting in large red cells with hypersegmented neutrophils

• pernicious anemia → autoimmune

  • antibodies against parietal cells and intrinsic factor, so B12 cannot be absorbed

• B12 deficiency damages nerves

  • numbness, tingling, poor balance, memory loss

  • folate alone can correct the anemia while nerve damage progresses

• at risk — long-term metformin or proton pump inhibitors, vegan diet, gastric bypass, older age

• oral findings —

  • beefy red, smooth burning tongue

  • aphthous ulcers

  • altered taste

• avoid nitrous oxide for B12 deficiency

  • NO inactivates cobalamin/B12 and may worsen deficiency

sickle cell disease

normocytic anemia, where valine replaces glutamic acid in β-globulin

• sickle cell disease when two copies are mutated; sickle cell trait when one copy is mutated

  • sickle cell trait usually asymptomatic

• triggers — low oxygen, dehydration, infection, cold, acidosis, stress

• effects —

  • hemolysis → anemia, jaundice, gallstones

  • blocked vessels → pain crises, acute chest syndrome, stroke, dactylitis

  • repeated infarction causes functional loss of spleen

    • results in increased infections with encapsulated bacteria

• treatment —

  • hydroxyurea raises fetal hemoglobin

  • transfusion

  • stem cell transplant

• most common inherited blood disorder worldwide

  • sub-Saharan Africa → heterozygous genotype (HbAS)

    • survival advantage against malaria, less likely to develop severe complications from malria associated with majority of deaths

  • African, Mediterranean, South Asia, Middle Eastern individuals

• universal newborn screening in the US → most patients know their status

sickle cell disease in the dental chair

treat between crises, with short morning appointments and keep patient warm, hydrated, and calm

• NO acceptable with at least 50% oxygen

• local anesthetic with epinephrine is acceptable

• treat dental infections promply → infection can trigger crisis

• consult hematologist before surgery

• believe the pain

  • pain in different areas due to sickle cell deposition in different tissues

  • stop elective care and allow them to use their usual crisis plan if appropriate

  • refer to physician/ED when necessary

G6PD deficiency

normocytic anemia that is X-linked; most common enzyme deficiency worldwide

• G6PD makes NADPH, which keeps glutathione ready to neutralize oxidants

  • G6PD deficiency results in poor antioxidant protection, causing oxidative damage to RBCs and hemolysis

• oxidative stress causes Heinz bodies, which have denatured Hb

  • splenic macrophages remove damaged areas → bite cells

  • results in sudden hemolysis, dark urine, jaundice

• triggers — sulfonamides, dapsone, primaquine, high-dose aspirin, fava beans, infections

• in dental chair —

  • avoid prilocaine and topical benzocaine → risk of methemoglobinemia

  • methylene blue is the antidote → can cause hemolysis in G6PD deficiency

thalassemia

microcytic anemia, where too little ⍺- or β-globin is made

• more common with Mediterranean, Middle Eastern, African, and Southeast Asian ancestry

• bone marrow expands to compensate

  • chronic anemia causes body to make more RBCs, expanding marrow and bone

• clinical findings —

  • chipmunk facies → prominent maxilla and zygomas, flared maxillary incisors

  • hair-on-end skull → stepladder trabeculation of the jaws

• in dental chair —

  • watch for jaundice and infection

  • repeated transfusions cause iron overload

• may have protective effect against malaria

familial Mediterranean fever (FMF)

most common inherited autoinflammatory disease

• innnate sysem fires with no infection and no autoantibodies

• autosomal recessive, where MEFV gene encodes pyrin

  • mutations over-activate inflammasome to produce IL-1

• more common with Turkish, Armenian, Sephardic Jewish and Arab

  • carrier rates in some groups as high as 1 in 5

  • usually begins before 20 years

• clinical findings —

  • fever for 12-72 hr with painful serositis → abdomen, chest, joint

  • erysipelas-like rash on lower legs

  • during attack → neutrophilia, high CRP/ESR

• complications —

  • AA amyloidosis in the kidneys from years of serum amyloid A

  • nephrotic syndrome, then renal failure

• treatment —

  • lifelong colchicine → prevents attacks and amyloidosis

  • IL-1 blockers if colchicine fails

• in dental chair —

  • never prescribe clarithromycin or erythromycin with colchicine

    • blocks clearance and causes fatal toxicity

    • be cautious with azole antifungals

  • with amyloid kidney disease → avoid NSAIDs and adjuncts

  • on IL-1 blockers → signs of infection may be blunted

  • stress and infection can trigger attacks, so schedule elective care between attacks

aplastic vs myelophthisic anemia

both cause pancytopenia

• aplastic anemia — bone marrow stem cells stop producing

  • caused by immune attack, drugs, toxins, viruses

• myelophthisic anemia — bone marrow becomes replaced/infiltrated

  • examples — leukemia, myeloma, metastatic cancer

• in pancytopenia, every line fails

  • red cells → fatigue and pallor

  • platelets → petechiae, ecchymoses, gingival bleeding, epistaxis

  • neutrophils → infections and ulcers

• before dental treatment → medical consultation and CBC

when to postpone elective care for anemia

• postpone elective care if:

  • Hb < 11 g/dL with symptoms

  • shortness of breath at rest or with minimal exertion

  • abnormal heart rate

  • oxygen saturation < 91%

• refer when you find:

  • pallor, glossitis, or angular cheilitis without an explanation

  • iron deficiency in a man or menopausal woman

  • numbness or tingline with a sore tongue

  • jaundice or anemia with bleeding and infection

white cell count

• absolute neutrophil count — WBC x (% neutrophils + % bands)

  • > 2000/µL → routine care

  • 1000-2000 → clinical judgement; ask about antibiotic prophylaxis

  • < 1000 → defer elective care and consult

• platelet count — normal = 150,000-450,000/µL

  • > 50,000 → defer invasive care and consult

  • > 20,000 → spontaneous bleeding

• pattern to not miss → gingival enlargement + bleeding + bruising + fatigue

  • CBC and referral, not a cleaning/recall

  • lower neutrophil count can be normal → Duffy-null associated neutrophil count

patterns to recognize

• leukemic gingival infiltration — diffuse, boggy enlargement out of proportion to plaque

  • most typical of acute myeloid leukemia with monocytic features

  • same-day CBC and referral

• palatal petechiae — due to infectious mononucleosis, low platelets, trauma, forceful coughing, vomiting

  • ask and look for cause

  • amoxicillin during mononucleiosis often causes a rash that is not a true penicillin allergy

hemostasis steps

platelet problems bleed immediately from mucosae with petechiae; factor problems bleed later and deeper in joints, muscles, and sockets

1. platelet plug (seconds)

   • vasospasm causes platelets to adhere, activate, and aggregate

   • fails with — thrombocytopenia, aspirin, clopidogrel, von Willebrand disease

2. fibrin clot (minutes)

   • coagulation cascade generates thrombin

   • thrombin turns fibrinogen into a fibrin mesh

   • fails with — warfarin, direct oral anticoagulants (DOACs), heparain, hemophilia, liver disease

3. fibrinolysis (days)

   • plasmin dissolves the clot as the tissue heals

   • measured as D-dimer

   • too early → causes dry socket

     • blocked by tranexamic acid

primary hemostasis — platelet plug

1. adhesion — platelets stick

   • injury exposes collagen, which vWF binds

   • platelet GPIb binds vWF

   • defects → von Willebrand disease, Bernard-Soulier (GPIb)

     • vWF carries and protects factor VIII, which can prolong aPTT

2. activation — platelets signal

   • shape changes, releasing ADP and thromboxane A2

   • more platelets are recruited

   • drugs → aspirin (thromboxane), clopidogrel, prasugrel, ticagrelor (ADP receptor P2Y12)

3. aggregation — platelets link

   • GPIIa/IIIb binds fibrinogen

   • fibrinogen bridges platelet to platelet

   • defect → Glanzmann thrombasthenia (GPIIb/IIIa)

   • immune thrombocytopenia (ITP) → antibodies against GPIIb/IIIa (type II hypersensitivity)

secondary hemostasis — fibrin clot

1. initiation — tissue factor starts it

   • injury exposes tissue factor

   • tissue factor + factory VIIa activate X and IX

   • small amount of thrombin forms

2. amplification — thrombin recruits help

   • thrombin activates platelets and factors V, VIII, XI

3. propagation — thrombin burst

   • IXa + VIIIa activate X; Xa + Va make thrombin

   • fibrinogen becomes fibrin

   • factor XIII cross-links fibrin to form mesh

PT/INR + aPTT

• PT/INR → factor VII and common pathway (X, V, II, fibrinogen)

  • affected by warfarin, liver disease, vitamin K deficiency

• aPTT → factors XII, XI, IX, VIII, and common pathway

  • affected by heparin, hemophilia A and B

vitamin K

vitamin K-dependent factors include II, VII, IX, X and protein C and S

• warfarin blocks vitamin K recycling (VKORC1)

• factor VII has the shortest half-life, so INR rises first

• vitamin K deficiency → malabsorption, long-term broad-spectrum antibiotics, newborns

• natural anticoagulants:

  • antithrombin → inactivates thrombin and Xa

    • enhanced by heparin

  • proteins C and S → inactivate Va and VIIIa

  • tissue factor pathway inhibitor → turns off initiation

    • newer hemophilia drugs work by blocking these brakes

dissolving the clot — fibrinolysis

tissue plasminogen activator converts plasminogen to plasmin

• plasmin cuts fibrin into into fragments → forms D-dimer as product

  • elevated D-dimer means that clot is forming and breaking down somewhere, like in DVT, pulmonary embolism, DIC

• tranexamic acid blocks plasminogen from binding fibrin

  • used as 5% mouthwash or on gauze, after extractions in anticoagulated or hemophilic patients

• alveolar osteitis → fibrinolysis arriving too early

  • clot dissolves before granulation tissue can replace it

reading coagulation labs

bleeding time is obsolete, and reasoning should not be built around it because DOACs can change PT/PTT unpredictably

• platelet count — normal = 150,000-450,000/µL

  • measures amount of platelets

  • prolonged/abnormal with → ITP, leukemia, chemotherapy, aplastic anemia, liver disease, heparin-induced thrombocytopenia

• PT/INR — normal PT = 11.0-13.5; normal INR = 2.0-3.0

  • measure factor VII and common pathway

  • prolonged/abnormal with → warfarin, liver disease, vitamin K deficiency

• aPTT — normal = 25-35 s

  • measures factors XII, XI, IX, VIII, and common pathway

  • prolonged/abnormal with → heparin, hemophilia A and B, some von Willebrand disease

• platelet function (PFA-100) — laboratory-specific norms

  • measures whether platelets work

  • prolonged/abnormal with → aspirin, P2Y12 inhibitors, von Willebrand disease, kidney failure (uremia)

reading lab patterns

• low platelets; PT and aPTT normal → ITP, drug-induced, leukemia or marrow failure, heparin-induced thrombocytopenia

• PT/INR prolonged; aPTT normal → warfarin, early liver disease, vitamin K deficiency

• aPTT prolonged; PT normal → heparin, hemophilia A or B, von Willebrand disease

• PT and aPTT prolonged → advanced liver disease, DIC, severe vitamin K deficiency

• everything normal but pt bleeds → mild von Willebrand disease, aspirin or other antiplatelet drugs, kidney failure, vascular causes

places where bleeding can go wrong

1. vessels

   • scurvy → gingival swelling and bleeding

   • Ehlers-Danlos syndromes → affects collagen

   • hereditary hemorrhagic telangiectasia → telagiectasias of the lips and tongue, nosebleeds

     • recommended to have antibiotic prophylaxis before dental procedure to help prevent brain abscess

   • long-term corticosteroids

2. platelets

   • too few → ITP, leukemia, chemotherapy, drugs, heparin, enlarged spleen

   • not working → aspirin, P2Y12 inhibitors, kidney failure, von WIllebrand disease

3. factors

   • hemophilia A and B

   • von Willebrand disease

   • liver disease, vitamin K deficiency

   • warfarin, DOACs, heparin

   • DIC

von Willebrand disease

most common inherited bleeding disorder, up to 1 in 100 people and almost never diagnosed

• autosomal dominant → men and women affected

• von Willebrand factor functions — involved in primary and secondary hemostasis

  • glues platelets to collagen

  • carries and protects factor VIII

• clinical findings — mucosal bleeding

  • gingival bleeding, nosebleeds, heavy menstrual bleeding, prolonged bleeding after extractions

• treatment —

  • desmopressin (DDAVP) → released stored von Willebrand factor (type 1)

  • von Willebrand factor concentrate; tranexamic acid

  • consult hematologist before surgery; avoid NSAIDs

hemophilia A and B

X-linked recessive inheritance — hemophilia A = factor VIII deficiency; hemophilia B = factor IX deficiency

• severity follows factor level

  • severe (<1%), moderate (1-5%), mild (5-40%)

• bleeding pattern —

  • deep bleeding → joints (hemarthrosis), muscles

  • delayed oozing after extractions

• in dental chair — plan with the hemophilia treatment center

  • factor replacement before invasive care; tranexamic acid after

  • inferior alveolar nerve block without factor coverage risks a hematoma in pterygomandibular space that can compress the airway

    • prefer infiltration of intraligamentary injection when possible

  • avoid NSAIDs

  • prevention is the best treatment

• treatment —

  • replace the factor → recombinant factor VIII or IX

    • extended half-life products need fewer infusions

  • mimic the factor → emicizumab antibody that mimics factor VIIIa function

    • injected under the skin, weekly to monthly

    • falsely normalizes the aPTT, so normal aPTT does not mean normal clotting

  • release the brakes →

    • concizumab, marstacimab — blocks tissue factor pathway inhibitor

    • fitusiran — lowers antithrombin

    • gene therapy for hemophilia B

low platelet count disorders

• immune thrombocytopenia (ITP) — type II hypersensitivity, where antibodies target platelet GPIIb/IIIa and cause low platelet count

  • children → often follows viral infection, acute, often resolves

  • adults → often women, chronic

• heparin-induced thrombocytopenia — occurs 5-10 days after heparin, where platelets fall but patients clot

• clinical findings —

  • petechie and purpura, often on palate

  • gingival oozing and nosebleeds

  • bleeding starts immediately because it is a platelet pattern

common anticoagulants and antiplatelets

• vitamin K antagonist — warfarin

  • lowers factors II, VII, IX, X

  • labs → INR

  • dental approach → check INR, proceed if 3.5 or below

    • simple extractions can proceed with local hemostatic measures

• factor Xa inhibitors — apixaban, rivaroxaban, edoxaban

  • blocks factor Xa

  • dental approach → low risk, do not interrupt

• thrombin inhibitors — dabigatran

  • blocks thrombin

  • dental approach → low risk, do not interrupt

• heparins — enoxaparin, heparin

  • boost antithrombin

  • labs → aPTT

  • dental approach → usually short-term or in hospital, consult

• antiplatlets — aspirin, clopidogrel, prasugrel, ticagrelor

  • blocks COX-1 or ADP receptor

  • dental approach → continue, never stop dual therapy after a stent without cardiologist

warfarin

vitamin K antagonist that lowers factors II, VII, IX, X

• before treatment → INR within 24 hr

  • INR ≤ 3.5 can proceed with local measures

  • INR > 3.5 should be deferred and consulted with physician

• drugs that raise INR:

  • metronidazole

  • azole fungals → miconazole oral gel, fluconazole

  • erythromycin and clarithromycin

  • regular acetaminophen above 2g/day for several days

    • NSAIDS do not raise INR but add bleeding risk

direct oral anticoagulants (DOACs)

apixaban, rivaroxaban, edoxaban, dabigatran

• low bleeding risk → should not be interrupted

  • simple extractions of up to 3 teeth with a small wound

  • incision and drainage

  • scaling and root planing, restorations, endodontics

• higher bleeding risk → more than three extractions, flaps, biopsies, adjacent extractions with large wound

  • miss morning dose for apixaban and dabigatran

  • delay morning dose for rivaroxaban, edoxaban

  • confirm plan with prescriber

• have short half-life → effect fades within hours

• not measured by INR

• kidney disease prolongs effect (especially dabigatran)

• treat early in the day

antiplatelet drugs

aspirin, clopidogrel, prasugrel, ticagrelor

• continue for dental treatment, alone or together

  • expect more oozing with local measures to control it

• aspirin → effect lasts the entire lifespan of platelet (7-10 days)

• dual platelet therapy after coronary stent

  • typically 6-12 months after coronary stent

  • premature stopping risks stent thrombosis and potentially fatal MI

  • only cardiologist changes dosing

  • postpone elective surgery until dual therapy ends, if it can wait

local hemostatic measure

• before — morning appointment, early in the week

  • obtain current INR for warfarin

  • plan extent → start with up to 3 simple extractions

  • atraumatic technique

• during — firm pressure with damp gauze

  • sutures

  • oxidized cellulose, gelatin sponge, or collagen in socket

  • tranexamic acid 5% mouthwash or soaked gauze

• after — written instructions and phone number

  • acetaminophen for pain, not NSAIDs

  • no hot liquids or vigorous rinsing on day 1

  • review any new prescriptions for interactions