Hematologic problems inHematologic problems inpsychosomatic medicinepsychosomatic medicinepsychiatric clinic of north americapsychiatric clinic of north america

DR. Yasser Alhathial teamDR. Yasser Alhathial teamPresented by:Presented by:Ali bahathigAli bahathig

IntroductionIntroduction::

The consultationThe consultation psychiatric is frequently calledpsychiatric is frequently called assess patients in medical settingsassess patients in medical settings primary or secondary hematologic disordersprimary or secondary hematologic disorders.. This article adresses psychiatric issuesThis article adresses psychiatric issues → → specific to patients who have selectedspecific to patients who have selected hematologic disorders, including:hematologic disorders, including: → → B12B12 → → folate dificencyfolate dificency → → sikle cell diseasesikle cell disease → → HemophiliaHemophilia Finally, a review of hematologic side effects of Finally, a review of hematologic side effects of

psychotropic medication is also included. psychotropic medication is also included.

B12 & FOLATE DEFICIENCYB12 & FOLATE DEFICIENCY::

B12 & folate deficincy have similar consequences:B12 & folate deficincy have similar consequences: → → Nervous systemNervous system → → Megaloblastic anemiaMegaloblastic anemia Both are cofactors for conversion:Both are cofactors for conversion: Homocysteine → MethionineHomocysteine → Methionine Deficiency of both corrolate with:Deficiency of both corrolate with: ↑ ↑ Homocysteine levelHomocysteine level → → C.V.S, STROKE, DEMENTIA & C.V.S, STROKE, DEMENTIA & ALzheimer’s diseaseALzheimer’s disease ↑ ↑ Homocysteine level & ↓ of B12 & folate:Homocysteine level & ↓ of B12 & folate: also associared with depression.also associared with depression.

Vitamin B12Vitamin B12

Necessary coenzyme & cofactor in virous reaction:Necessary coenzyme & cofactor in virous reaction:

→ → synthesis of DNA + methioninesynthesis of DNA + methionine Epidemiologic studies:Epidemiologic studies:

→ → prevalence of about 20% in general populationprevalence of about 20% in general population

→ → number of geriatric individuals → even highernumber of geriatric individuals → even higher

→ → common in psychiatric populationscommon in psychiatric populations.. Pernicious anemia → B12 deficiencyPernicious anemia → B12 deficiency

→ → Autoimmune disorderAutoimmune disorder

→ → associated with other autoimmune disorder:associated with other autoimmune disorder:

→ → thyroiditis, DM, grave’s disease…….thyroiditis, DM, grave’s disease…….

Dietary B12 deficiency is rareDietary B12 deficiency is rare Food or oral-cobalamin malabsorption may caused Food or oral-cobalamin malabsorption may caused

by: by: H. pylori infectionH. pylori infection

Intestinal overgrowth → antibioticsIntestinal overgrowth → antibiotics

chronic use of metformin, antacids, H-2 chronic use of metformin, antacids, H-2 blocker, blocker,

PPI, alcoholism and gastric surgeryPPI, alcoholism and gastric surgery Vitamin B12 Malabsorption results from:Vitamin B12 Malabsorption results from:

→ → GastrectomyGastrectomy

→ → Ileal diseasesIleal diseases

→ → Bowel resectionBowel resection

→ → Crohn’s diseaseCrohn’s disease

Clinical ManifestationClinical Manifestation::

Hematologic manifestation:Hematologic manifestation:

megaloblastic anemiamegaloblastic anemia

macrocytosis with hypersegmented macrocytosis with hypersegmented polymorphonuclear leuckocytespolymorphonuclear leuckocytes

thrombocytopeniathrombocytopenia

leukopenia and pancytopenialeukopenia and pancytopenia Gastrointestinal manifestation:Gastrointestinal manifestation:

intestinal metaplasia intestinal metaplasia

Hunter’s glossitisHunter’s glossitis

Diarrhea and jaundice.Diarrhea and jaundice.

Neuropschiatric manifestation:Neuropschiatric manifestation:

→ → common in B12 deficiency → in the elderlycommon in B12 deficiency → in the elderly

→ → may precede hematologic signsmay precede hematologic signs

→ → symmetrical peripheral neuropathysymmetrical peripheral neuropathy

→ → paresthesias & numbnessparesthesias & numbness

→ → subacute combined degeneration (SCD)subacute combined degeneration (SCD)

→ → less commonless common

→ → posterior & lateral column disruptionposterior & lateral column disruption

→ → loss of vibration & position senseloss of vibration & position sense

→ → ataxia, weaknees & spasticityataxia, weaknees & spasticity

rare manifestation: optic neuritis or atrophyrare manifestation: optic neuritis or atrophy

& incontinence& incontinence

Psychiatric manifestationPsychiatric manifestation::

→ → mood changesmood changes

→ → psychosispsychosis

→ → cognitive impairmentcognitive impairment

→ → obsessive – compulsive disorderobsessive – compulsive disorder B12 deficiency is a common cause ofB12 deficiency is a common cause of

→ → potentially reversible dementia &potentially reversible dementia &

confusionconfusion

Diagnosis and treatmentDiagnosis and treatment::

Low normal serum B12 + megaloblastic anemiaLow normal serum B12 + megaloblastic anemia

or or typical neuropsychiatric findingstypical neuropsychiatric findings

→ → further investigation further investigation Low normal level between 150ng ⁄L to 200ng ⁄ LLow normal level between 150ng ⁄L to 200ng ⁄ L Intrinstic factor Ab, serum gastrin:Intrinstic factor Ab, serum gastrin:

→ → Pernicious anemiaPernicious anemia Treatment recommendationTreatment recommendation::

1000 microgram IM of hydroxycobalamin or 1000 microgram IM of hydroxycobalamin or cyanocobalamin daily for 1 ⁄ 52cyanocobalamin daily for 1 ⁄ 52

then maintenence dose 1 ⁄ 12 or Q 3 ⁄ 52then maintenence dose 1 ⁄ 12 or Q 3 ⁄ 52 Oral replacement also is effectiveOral replacement also is effective

Remission is typically achived in weeksRemission is typically achived in weeks But, continued maintenance therpy is But, continued maintenance therpy is

recommendedrecommended

→ → replete body storesreplete body stores

→ → maintain longer period of remmsionmaintain longer period of remmsion Significant improvement of neuropsychiatric Significant improvement of neuropsychiatric

function has been shown after B12 adminstration.function has been shown after B12 adminstration. Degree of recovery → symptom severityDegree of recovery → symptom severity Adminstration of folate only to correct macrocytic Adminstration of folate only to correct macrocytic

anemia (unrecognized B12 deficiency )anemia (unrecognized B12 deficiency )

→ → will reverse the hematologic abnormalitieswill reverse the hematologic abnormalities

→ → but neurologic impairment may continuebut neurologic impairment may continue

→ → leading to irreversible deficitsleading to irreversible deficits

Folic acidFolic acid::

Folate is important in mood & cognition, brain Folate is important in mood & cognition, brain growth, differentiation, development & repair.growth, differentiation, development & repair.

These mechanisms:These mechanisms:

→ → nucleotide synthesisnucleotide synthesis

→ → DNA transcription & integrityDNA transcription & integrity Folate may protect agnist:Folate may protect agnist:

→ → certain cancerscertain cancers

→ → heart diseaseheart disease

→ → birth defectsbirth defects

→ → dementiadementia Presumably via the lowering homocysteinePresumably via the lowering homocysteine

Folate deficiency:Folate deficiency:

→ → inadequate diet, alcoholism, chronic illnessinadequate diet, alcoholism, chronic illness

→ → drugs ( phenytoin, valproic acid, lamotriginedrugs ( phenytoin, valproic acid, lamotrigine

barbiturates, oral contraceptive )barbiturates, oral contraceptive )

→ → malabsorptionmalabsorption More common in the elderlyMore common in the elderly More prevalent in psychiatric inpatients compared More prevalent in psychiatric inpatients compared

with patients without psychiatric illnesswith patients without psychiatric illness

(controlling for drug & alcohol abuse)(controlling for drug & alcohol abuse) One third of psychiatric patients, especially withOne third of psychiatric patients, especially with

depressiondepression

Clinical manifestationsClinical manifestations : :

Symptoms of folate deficiency are similar of B12 Symptoms of folate deficiency are similar of B12 SCD is specific to B12 deficiencySCD is specific to B12 deficiency Depression is more common in folate deficiencyDepression is more common in folate deficiency Insufficient folate during conception & eraly Insufficient folate during conception & eraly

pregnancy results:pregnancy results:

neural tube defects (NTD)neural tube defects (NTD) Folate deficiency is invariably accompanied by:Folate deficiency is invariably accompanied by:

↑ ↑ Plasma homocysteine levelPlasma homocysteine level

↑ ↑ Risk CVS disease,Risk CVS disease,

DementiaDementia

DepressionDepression

Diagnosis & treatmentDiagnosis & treatment::

Low RBC folate + ↑ plasma homocysteineLow RBC folate + ↑ plasma homocysteine

→ → is good standard for the diagnosisis good standard for the diagnosis

more accurate than measuring serum folate alonemore accurate than measuring serum folate alone No clear guidelines for the dose or durationNo clear guidelines for the dose or duration

→ → folate therapy for nervous system disorderfolate therapy for nervous system disorder Treatment is recommended for at least 6 monthsTreatment is recommended for at least 6 months To ↓ risk of NTDs:To ↓ risk of NTDs:

0.4 mg daily is recommended0.4 mg daily is recommended for woman at high risk:for woman at high risk:

4-5 mg dialy is recommended4-5 mg dialy is recommended

→ → one month at least prior to conceptionone month at least prior to conception

→ → through at least first trimester of pregnancythrough at least first trimester of pregnancy

In depressed patients:In depressed patients:

→ → low folate levels → higher levels of depressionlow folate levels → higher levels of depression

→ → less likely to respond to antidepressantsless likely to respond to antidepressants Coppen showed that supplementation of:Coppen showed that supplementation of:

fluoxetine + folic acid fluoxetine + folic acid

→ → improved antidepressant responseimproved antidepressant response

→ → concurrent ↓ in plasma homocysteine levelconcurrent ↓ in plasma homocysteine level

→ → not necessarily to ↑ plasma folate levelnot necessarily to ↑ plasma folate level

Sickle cell disease (SCD)Sickle cell disease (SCD):: SCD is the most common hemoglobinopathySCD is the most common hemoglobinopathy The vaso-occulsive crisis is the hallmark of SCDThe vaso-occulsive crisis is the hallmark of SCD → → acute episodes of severe painacute episodes of severe pain → → extreme of temperature, infectious illness, extreme of temperature, infectious illness, → → dehydration and physical exertion may dehydration and physical exertion may → → precipitate crises but,precipitate crises but, majority of crises → without an identifiable causemajority of crises → without an identifiable cause Vaso-occulsive produce:Vaso-occulsive produce: → → acute pain → in short termacute pain → in short term → → end-organ damage → in long termend-organ damage → in long term ( bone, kidney, lungs, eyes & brain)( bone, kidney, lungs, eyes & brain) Many patients suffer from chronic painMany patients suffer from chronic pain as result of avascular necrosis or leg ulceras result of avascular necrosis or leg ulcer

The neuropsychiatric manifestation of SCDThe neuropsychiatric manifestation of SCD

can be grouped in three main categories:can be grouped in three main categories:

→ → 1- depression and anxiety1- depression and anxiety

→ → 2- problems with substance abuse 2- problems with substance abuse

& dependence& dependence

→ → 3- central nervous system damage3- central nervous system damage These issues are further complicated by theThese issues are further complicated by the

poor psychosocial circumstances poor psychosocial circumstances

Depression and anxietyDepression and anxiety::

Prevalence of depression is about 26%Prevalence of depression is about 26% Anxiety disorders have been reported to be 7.1%Anxiety disorders have been reported to be 7.1% Children with SCD have ↑ prevalence:Children with SCD have ↑ prevalence:

excessive fatigue, physical complaints & impaired excessive fatigue, physical complaints & impaired

self-esteemself-esteem These feeling ariseThese feeling arise: :

→ → frequent hospitalizationfrequent hospitalization

→ → absences from schoolabsences from school

→ → inability to experience a normal childhood inability to experience a normal childhood

Adults with SCD faceAdults with SCD face::

→ → physical deformities + stigma of addictionphysical deformities + stigma of addiction

→ → the consequences of facing these stigmathe consequences of facing these stigma::

self-deprivation, self-hate, suspiciousness,self-deprivation, self-hate, suspiciousness,

depression and anxietydepression and anxiety Physical deformitiesPhysical deformities: :

→ → delayed growthdelayed growth

→ → chronic hemolysis & vaso-occlusionchronic hemolysis & vaso-occlusion

→ → problem with self-esteemproblem with self-esteem

→ → dissatisfaction with body imagedissatisfaction with body image

→ → social isolationsocial isolation

→ → participation in athletic is limited participation in athletic is limited

Chronic & acute painChronic & acute pain::

Patients experiences 0.8% episodes per year.Patients experiences 0.8% episodes per year. However, 1% of patient experiences more than 6 However, 1% of patient experiences more than 6

episodes per year.episodes per year. Nature of pain, which has been reported to be as Nature of pain, which has been reported to be as

severe as childbirthsevere as childbirth In last 15 years, opioid treatment has been used In last 15 years, opioid treatment has been used

widely for SCD painwidely for SCD pain

→ → control pain control pain

→ → improve function capacityimprove function capacity

→ → decrease hospitalizationdecrease hospitalization Substance dependence & addiction behaviorsSubstance dependence & addiction behaviors

difficult to define in any chronic pain condition difficult to define in any chronic pain condition

Few studies that address addiction in SCD report a Few studies that address addiction in SCD report a low prevalencelow prevalence

Despite this lack of evidence in medical literatureDespite this lack of evidence in medical literature medical practitioners often overestimate addictionmedical practitioners often overestimate addiction Studies demonstrateStudies demonstrate:: → → 63% of nurse believe addiction is prevalent 63% of nurse believe addiction is prevalent → → 53% of ER physicians53% of ER physicians → → 23% of hematologist though more than 20% 23% of hematologist though more than 20% Fear of iatrogenic addictionFear of iatrogenic addiction, , → → physicians may under treat pain physicians may under treat pain

As a result of under treatment, patient may develop As a result of under treatment, patient may develop a pseudo-addcitiona pseudo-addcition

(addiction like behavior occur → inadequate pain)(addiction like behavior occur → inadequate pain) May seek illegal narcotics to manage their painMay seek illegal narcotics to manage their pain → → long-term problems with true addictionlong-term problems with true addiction Some patients may inappropriately use opioid in Some patients may inappropriately use opioid in

non pain symptomsnon pain symptoms:: → → insomniainsomnia → → depressiondepression → → anxietyanxiety In recent studies, 31.4% of adult SCD were found to In recent studies, 31.4% of adult SCD were found to

abuse alcohol abuse alcohol

Central nervous system Central nervous system damagedamage::

Brain disease from SCD complicationBrain disease from SCD complication

begins early in life → neurocognitive dysfunctionbegins early in life → neurocognitive dysfunction 25-33% of children with SCD have CNS effects25-33% of children with SCD have CNS effects Seizures occur in 12-14% of SCD patientsSeizures occur in 12-14% of SCD patients

→ → often lead to strokeoften lead to stroke CVA occur in 10-15% of SCD childrenCVA occur in 10-15% of SCD children These demonstrateThese demonstrate::

→ → intellectual deficitsintellectual deficits

(ranging from borderline to moderate MR)(ranging from borderline to moderate MR)

→ → reduced language functionreduced language function

→ → problem with adjustmentproblem with adjustment

Cognitive deficits in SCD children can lead to:Cognitive deficits in SCD children can lead to:

→ → educational problemseducational problems

→ → Intellectual impairmentIntellectual impairment

→ → verbal problemsverbal problems

→ → problems with attention and concentrationproblems with attention and concentration

→ → dementia later in lifedementia later in life

HemophiliaHemophilia::

Hemophilia is a bleeding disorderHemophilia is a bleeding disorder

→ → deficiency of the coagulation factorsdeficiency of the coagulation factors Hemophilia A (factor VIII)Hemophilia A (factor VIII) Hemophilia B (factor IX)Hemophilia B (factor IX)

→ → well known inherited bleeding disorderswell known inherited bleeding disorders

→ → clinically, indistinguishable from one anotherclinically, indistinguishable from one another X-linked & mainly affects malesX-linked & mainly affects males ClassificationClassification: : severesevere

moderatemoderate

mildmild Useful for predicting bleeding tendency and Useful for predicting bleeding tendency and

prognosis prognosis

Severe hemophilia ( < 1% clotting factor)Severe hemophilia ( < 1% clotting factor) bleed spontaneously into:bleed spontaneously into: → → joints joints → → muscles muscles → → soft tissuessoft tissues → → body cavitiesbody cavities Neonatal periodsNeonatal periods:: → →1-4% risk of developing intracranial1-4% risk of developing intracranial hemorrhagehemorrhage Most children are asymptomaticMost children are asymptomatic → → until they start crawlinguntil they start crawling → → bruise easily and bleed following minorbruise easily and bleed following minor injuriesinjuries

((family of these children → child abusefamily of these children → child abuse))

By age of 4 years most children experience By age of 4 years most children experience → → bleed into a jointbleed into a joint Adult experience recurrent bleed intoAdult experience recurrent bleed into:: → → large joints & muscleslarge joints & muscles → → joint bleeding →severe acute painjoint bleeding →severe acute pain Repeated bleed lead to destruction:Repeated bleed lead to destruction: → → cartilagecartilage → → bone bone → → muscle wastingmuscle wasting → → chronic painchronic pain

Moderate hemophilia (1-5% clotting factor):Moderate hemophilia (1-5% clotting factor):

→ → typically diagnosed by the age of 5 yearstypically diagnosed by the age of 5 years

→ → bleeding episodes occur less frequentlybleeding episodes occur less frequently Mild hemophilia (> than 5% clotting factor)Mild hemophilia (> than 5% clotting factor)

→ → diagnosed later following trauma, tooth extractiondiagnosed later following trauma, tooth extraction

or surgeryor surgery

→ → spontaneous bleeding is rarespontaneous bleeding is rare In 1990s, more than 80% of severe hemophilia In 1990s, more than 80% of severe hemophilia

patients were infected with viral illnessespatients were infected with viral illnesses

→ → HIV, hepatitis B & C HIV, hepatitis B & C

In children & adolescents higher rate of anxiety In children & adolescents higher rate of anxiety disorder have been reported in hemophilic than disorder have been reported in hemophilic than asthmaticsasthmatics

Physician are reluctant to prescribe opiatesPhysician are reluctant to prescribe opiates

→ → despite the severe paindespite the severe pain Individual, group and family psychotherapyIndividual, group and family psychotherapy

→ → useful psychotherapeuticuseful psychotherapeutic Caution is needed in prescribing psychotropicCaution is needed in prescribing psychotropic

→ → dose of antidepressant, antipsychotic & opiatedose of antidepressant, antipsychotic & opiate

→ → reduced to compensate for hepatic impairmentreduced to compensate for hepatic impairment

→ → may ↑ the risk of bleeding may ↑ the risk of bleeding

Hemophilia & AIDS patients face many stressorsHemophilia & AIDS patients face many stressors::

→ → opportunistic infectionopportunistic infection

→ → physical wasting, declining health, chronic painphysical wasting, declining health, chronic pain

→ → CNS complicationsCNS complications…….……. Mother of HIV +ve hemophilic more distressed than Mother of HIV +ve hemophilic more distressed than

mother of HIV –ve hempphilicmother of HIV –ve hempphilic After death from AIDS, bereaved families:After death from AIDS, bereaved families:

→ → extensive psychologic counseling & supportextensive psychologic counseling & support Study in Japan foundStudy in Japan found → 7-9 years after death → 7-9 years after death

bereaved family membersbereaved family members → deep sorrow & grief → deep sorrow & grief

→ → regret, anger, guiltregret, anger, guilt 70% of bereaved family70% of bereaved family → restricting daily activities → restricting daily activities 50% of bereaved family50% of bereaved family → mental heath problems → mental heath problems

Hematologic side effects & drug Hematologic side effects & drug interaction of psychotropic agentsinteraction of psychotropic agents::

Antipsychotic:Antipsychotic:

→ → aripiprazole & ziprasidone aripiprazole & ziprasidone

→ → do not have → hematologic side effectsdo not have → hematologic side effects Agranulocytosis is rare → most common & seriousAgranulocytosis is rare → most common & serious Low potency > high potencyLow potency > high potency Clozapine causes agrnulocytosis → 0.8 % Clozapine causes agrnulocytosis → 0.8 %

→ → highest risk in → first 6 months → ↓ significantlyhighest risk in → first 6 months → ↓ significantly

→ → case fatality rate → 4.2-16%case fatality rate → 4.2-16%

(growth stimulating factor GSF)(growth stimulating factor GSF)

→ → Weekly WBC count is necessaryWeekly WBC count is necessary

If WBC count < 2000/mm If WBC count < 2000/mm

or absolute neutrophil count < 1000/mmor absolute neutrophil count < 1000/mm

→ → immediate cessation of clozapineimmediate cessation of clozapine Stopping clozapine → recovery in WBC in 3 weeksStopping clozapine → recovery in WBC in 3 weeks Mortality risk associated with agranulocytosisMortality risk associated with agranulocytosis

→ → ↑ ↑ if infection occur while still on the drugif infection occur while still on the drug As Clozapine cause bone marrow suppressionAs Clozapine cause bone marrow suppression::

→ → GSFs → normal bone marrow productionGSFs → normal bone marrow production Potential hematologic side effectsPotential hematologic side effects::

→ → aplastic anemia, neutropenia, eosinophiliaaplastic anemia, neutropenia, eosinophilia

→ → thrombocytopenia thrombocytopenia

Antidepressants:Antidepressants: SSRIs inhibit platelet function → bruising & bleedingSSRIs inhibit platelet function → bruising & bleeding

→ → especially → with aspirin or NSAIDsespecially → with aspirin or NSAIDs SSRIs:SSRIs:

↑ ↑ CNS serotoninCNS serotonin

↓ ↓ platelets serotonin → ↓ platelets aggregationplatelets serotonin → ↓ platelets aggregation Upper GIT bleeding may occur at a frequency fromUpper GIT bleeding may occur at a frequency from

1 in100 to 1 in 1000 patient-year exposure to high-1 in100 to 1 in 1000 patient-year exposure to high-affinity drugs with SSRIs → elderlyaffinity drugs with SSRIs → elderly

Caution is advised in patient at high risk of GI Caution is advised in patient at high risk of GI bleedingbleeding

→ → consider prescribing a antidepressantconsider prescribing a antidepressant

Patients taking SSRIs should generally usePatients taking SSRIs should generally use

→ → smaller doses or avoid aspirin or NSAIDssmaller doses or avoid aspirin or NSAIDs Risk of GI bleeding Risk of GI bleeding

→ → highest among patients on both SSRIs & NSAIDshighest among patients on both SSRIs & NSAIDs While the evidence to dateWhile the evidence to date

→ → SSRIs do not cause intracranial bleedingSSRIs do not cause intracranial bleeding

→ → there is a report that patients takingthere is a report that patients taking

→ → SSRIs along with statinsSSRIs along with statins

→ → higher risk for subarachnoid hemorrhage higher risk for subarachnoid hemorrhage

While some reviews have concluded there is While some reviews have concluded there is

→ → no ↑ risk of combining SSRIs with warfarinno ↑ risk of combining SSRIs with warfarin

→ → case reports of bleeding with concomitant usecase reports of bleeding with concomitant use

of SSRIs & warfarinof SSRIs & warfarin Fluoxetine is the most commonly offending agents.Fluoxetine is the most commonly offending agents. Interactions between warfarin & SSRIsInteractions between warfarin & SSRIs

→ → potentially serious consequencespotentially serious consequences

→ → enhanced or reduced anticoagulant activityenhanced or reduced anticoagulant activity The possible mechanisms → cytochrome p450The possible mechanisms → cytochrome p450 Fluoxetine, fluvoxamine, paroxetine Fluoxetine, fluvoxamine, paroxetine

→ → highest potential → interactionhighest potential → interaction Citalopram, nefazodone, sertralineCitalopram, nefazodone, sertraline

→ → relatively less likely to interact with warfarin relatively less likely to interact with warfarin

Agrnulocytosis due to TCAs is a rareAgrnulocytosis due to TCAs is a rare Idiosyncratic condition → bone marrow toxicityIdiosyncratic condition → bone marrow toxicity Lower frequency than antipsychoticLower frequency than antipsychotic Agrnulocytosis has been associated:Agrnulocytosis has been associated:

→ → imipramineimipramine

→ → clomipramineclomipramine

→ → desipraminedesipramine Clomipramine-induced agranulocytosisClomipramine-induced agranulocytosis

→ → recombinant granulocyte colony-stimulating factor recombinant granulocyte colony-stimulating factor

BenzodiazepinesBenzodiazepines:: Agrnulocytosis has rarely been reportedAgrnulocytosis has rarely been reported No causal relationship has been establishedNo causal relationship has been established No relationship between daily dose or total No relationship between daily dose or total

cumulative dose & occurrence of hematologic side cumulative dose & occurrence of hematologic side effectseffects

LithiumLithium:: Lithium stimulate leukocytosis with true proliferative Lithium stimulate leukocytosis with true proliferative

responseresponse In patients on lithium therapy:In patients on lithium therapy:

documented increases in the:documented increases in the:

→ → number of plateletnumber of platelet

→ → platelet serotonin & histamine levelsplatelet serotonin & histamine levels Lithium-induced hematologic side effectsLithium-induced hematologic side effects

→ → manage hematologic toxicities associated withmanage hematologic toxicities associated with

other agent & disorderother agent & disorder Patients with persistent leucopenia Patients with persistent leucopenia

&thrombocytopenia&thrombocytopenia

following chemotherapy or radiotherapyfollowing chemotherapy or radiotherapy

→ → can be treated with lithiumcan be treated with lithium

Anticonvulsants & mood stabilizersAnticonvulsants & mood stabilizers:: Carbamazepine should be avoidedCarbamazepine should be avoided

→ → history of bone marrow depressionhistory of bone marrow depression

→ → Produce a transient reduction in WBCs Produce a transient reduction in WBCs

→ →10% of patients during first 4 months10% of patients during first 4 months Very rarely it causes potentially:Very rarely it causes potentially:

→ → fatal agranulocytosisfatal agranulocytosis

→ → aplastic anemiaaplastic anemia Baseline CBC count → advised before startingBaseline CBC count → advised before starting If the WBCs count drop below 3500/mmIf the WBCs count drop below 3500/mm

→ → carbamazepine should be stopped carbamazepine should be stopped

Carbamazepine stimulate it’s own metabolismCarbamazepine stimulate it’s own metabolism

→ → after being taken for a period of timeafter being taken for a period of time

→ → suddenly decreasesuddenly decrease Induce hepatic metabolismInduce hepatic metabolism

→ → reduces the anticoagulant effect of warfarinreduces the anticoagulant effect of warfarin

→ → Carbamazepine level & INR will need to beCarbamazepine level & INR will need to be

monitored frequentlymonitored frequently Neutropenia, thrombocytopenia & macrocytic Neutropenia, thrombocytopenia & macrocytic

anemiaanemia

→ → have been associated with valproatehave been associated with valproate Lamotrigine may also cause agrnulocytosisLamotrigine may also cause agrnulocytosis All anticonvulsants should be discontinued whenAll anticonvulsants should be discontinued when

the WBCs count drop below 3000/mmthe WBCs count drop below 3000/mm

Think youThink you