Hematologic problems in

psychosomatic medicine
psychiatric clinic of north america

DR. Yasser Alhathial team

:Presented by
Ali bahathig
:Introduction
 The consultation psychiatric is frequently called
assess patients in medical settings
primary or secondary hematologic disorders.
 This article adresses psychiatric issues
→ specific to patients who have selected
hematologic disorders, including:
→ B12
→ folate dificency
→ sikle cell disease
→ Hemophilia
 Finally, a review of hematologic side effects of
psychotropic medication is also included.
:B12 & FOLATE DEFICIENCY
 B12 & folate deficincy have similar consequences:
→ Nervous system
→ Megaloblastic anemia
 Both are cofactors for conversion:
Homocysteine → Methionine
 Deficiency of both corrolate with:
↑ Homocysteine level
→ C.V.S, STROKE, DEMENTIA &
ALzheimer’s disease
 ↑ Homocysteine level & ↓ of B12 & folate:
also associared with depression.
Vitamin B12
 Necessary coenzyme & cofactor in virous reaction:
→ synthesis of DNA + methionine
 Epidemiologic studies:
→ prevalence of about 20% in general population
→ number of geriatric individuals → even higher
→ common in psychiatric populations.
 Pernicious anemia → B12 deficiency
→ Autoimmune disorder
→ associated with other autoimmune disorder:
→ thyroiditis, DM, grave’s disease…….
 Dietary B12 deficiency is rare
 Food or oral-cobalamin malabsorption may caused
by: H. pylori infection
Intestinal overgrowth → antibiotics
chronic use of metformin, antacids, H-2
blocker,
PPI, alcoholism and gastric surgery
 Vitamin B12 Malabsorption results from:
→ Gastrectomy
→ Ileal diseases
→ Bowel resection
→ Crohn’s disease
:Clinical Manifestation
 Hematologic manifestation:
megaloblastic anemia
macrocytosis with hypersegmented
polymorphonuclear leuckocytes
thrombocytopenia
leukopenia and pancytopenia
 Gastrointestinal manifestation:
intestinal metaplasia
Hunter’s glossitis
Diarrhea and jaundice.
 Neuropschiatric manifestation:
→ common in B12 deficiency → in the elderly
→ may precede hematologic signs
→ symmetrical peripheral neuropathy
→ paresthesias & numbness
→ subacute combined degeneration (SCD)
→ less common
→ posterior & lateral column disruption
→ loss of vibration & position sense
→ ataxia, weaknees & spasticity

rare manifestation: optic neuritis or atrophy

& incontinence
 Psychiatric manifestation:
→ mood changes
→ psychosis
→ cognitive impairment
→ obsessive – compulsive disorder
 B12 deficiency is a common cause of
→ potentially reversible dementia &
confusion
:Diagnosis and treatment
 Low normal serum B12 + megaloblastic anemia
or typical neuropsychiatric findings
→ further investigation
 Low normal level between 150ng ⁄L to 200ng ⁄ L
 Intrinstic factor Ab, serum gastrin:
→ Pernicious anemia
 Treatment recommendation:
1000 microgram IM of hydroxycobalamin or
cyanocobalamin daily for 1 ⁄ 52
then maintenence dose 1 ⁄ 12 or Q 3 ⁄ 52
 Oral replacement also is effective
 Remission is typically achived in weeks
 But, continued maintenance therpy is
recommended
→ replete body stores
→ maintain longer period of remmsion
 Significant improvement of neuropsychiatric
function has been shown after B12 adminstration.
 Degree of recovery → symptom severity
 Adminstration of folate only to correct macrocytic
anemia (unrecognized B12 deficiency )
→ will reverse the hematologic abnormalities
→ but neurologic impairment may continue
→ leading to irreversible deficits
:Folic acid
 Folate is important in mood & cognition, brain
growth, differentiation, development & repair.
 These mechanisms:
→ nucleotide synthesis
→ DNA transcription & integrity
 Folate may protect agnist:
→ certain cancers
→ heart disease
→ birth defects
→ dementia
 Presumably via the lowering homocysteine
 Folate deficiency:
→ inadequate diet, alcoholism, chronic illness
→ drugs ( phenytoin, valproic acid, lamotrigine
barbiturates, oral contraceptive )
→ malabsorption
 More common in the elderly
 More prevalent in psychiatric inpatients compared
with patients without psychiatric illness
(controlling for drug & alcohol abuse)
 One third of psychiatric patients, especially with
depression
:Clinical manifestations
 Symptoms of folate deficiency are similar of B12
 SCD is specific to B12 deficiency
 Depression is more common in folate deficiency
 Insufficient folate during conception & eraly
pregnancy results:
neural tube defects (NTD)
 Folate deficiency is invariably accompanied by:
↑ Plasma homocysteine level
↑ Risk CVS disease,
Dementia
Depression
:Diagnosis & treatment
 Low RBC folate + ↑ plasma homocysteine
→ is good standard for the diagnosis
more accurate than measuring serum folate alone
 No clear guidelines for the dose or duration
→ folate therapy for nervous system disorder
 Treatment is recommended for at least 6 months
 To ↓ risk of NTDs:
0.4 mg daily is recommended
 for woman at high risk:
4-5 mg dialy is recommended
→ one month at least prior to conception
→ through at least first trimester of pregnancy
 In depressed patients:
→ low folate levels → higher levels of depression
→ less likely to respond to antidepressants
 Coppen showed that supplementation of:
fluoxetine + folic acid
→ improved antidepressant response
→ concurrent ↓ in plasma homocysteine level
→ not necessarily to ↑ plasma folate level
:Sickle cell disease (SCD)
 SCD is the most common hemoglobinopathy
 The vaso-occulsive crisis is the hallmark of SCD
→ acute episodes of severe pain
→ extreme of temperature, infectious illness,
→ dehydration and physical exertion may
→ precipitate crises but,
majority of crises → without an identifiable cause
 Vaso-occulsive produce:
→ acute pain → in short term
→ end-organ damage → in long term
( bone, kidney, lungs, eyes & brain)
 Many patients suffer from chronic pain
as result of avascular necrosis or leg ulcer
 The neuropsychiatric manifestation of SCD
can be grouped in three main categories:
→ 1- depression and anxiety
→ 2- problems with substance abuse
& dependence
→ 3- central nervous system damage
 These issues are further complicated by the
poor psychosocial circumstances
:Depression and anxiety
 Prevalence of depression is about 26%
 Anxiety disorders have been reported to be 7.1%
 Children with SCD have ↑ prevalence:
excessive fatigue, physical complaints & impaired
self-esteem
 These feeling arise:
→ frequent hospitalization
→ absences from school
→ inability to experience a normal childhood
 Adults with SCD face:
→ physical deformities + stigma of addiction
→ the consequences of facing these stigma:
self-deprivation, self-hate, suspiciousness,
depression and anxiety
 Physical deformities:
→ delayed growth
→ chronic hemolysis & vaso-occlusion
→ problem with self-esteem
→ dissatisfaction with body image
→ social isolation
→ participation in athletic is limited
:Chronic & acute pain
 Patients experiences 0.8% episodes per year.
 However, 1% of patient experiences more than 6
episodes per year.
 Nature of pain, which has been reported to be as
severe as childbirth
 In last 15 years, opioid treatment has been used
widely for SCD pain
→ control pain
→ improve function capacity
→ decrease hospitalization
 Substance dependence & addiction behaviors
difficult to define in any chronic pain condition
 Few studies that address addiction in SCD report a
low prevalence
 Despite this lack of evidence in medical literature
medical practitioners often overestimate addiction
 Studies demonstrate:
→ 63% of nurse believe addiction is prevalent
→ 53% of ER physicians
→ 23% of hematologist though more than 20%
 Fear of iatrogenic addiction,
→ physicians may under treat pain
 As a result of under treatment, patient may develop
a pseudo-addcition
(addiction like behavior occur → inadequate pain)
 May seek illegal narcotics to manage their pain
→ long-term problems with true addiction
 Some patients may inappropriately use opioid in
non pain symptoms:
→ insomnia
→ depression
→ anxiety
 In recent studies, 31.4% of adult SCD were found to
abuse alcohol
Central nervous system
:damage
 Brain disease from SCD complication
begins early in life → neurocognitive dysfunction
 25-33% of children with SCD have CNS effects
 Seizures occur in 12-14% of SCD patients
→ often lead to stroke
 CVA occur in 10-15% of SCD children
 These demonstrate:
→ intellectual deficits
(ranging from borderline to moderate MR)
→ reduced language function
→ problem with adjustment
 Cognitive deficits in SCD children can lead to:
→ educational problems
→ Intellectual impairment
→ verbal problems
→ problems with attention and concentration
→ dementia later in life
:Hemophilia
 Hemophilia is a bleeding disorder
→ deficiency of the coagulation factors
 Hemophilia A (factor VIII)
 Hemophilia B (factor IX)
→ well known inherited bleeding disorders
→ clinically, indistinguishable from one another
 X-linked & mainly affects males
 Classification: severe
moderate
mild
 Useful for predicting bleeding tendency and
prognosis
 Severe hemophilia ( < 1% clotting factor)
bleed spontaneously into:
→ joints
→ muscles
→ soft tissues
→ body cavities
 Neonatal periods:
→1-4% risk of developing intracranial
hemorrhage
 Most children are asymptomatic
→ until they start crawling
→ bruise easily and bleed following minor
injuries
(family of these children → child abuse)
 By age of 4 years most children experience
→ bleed into a joint
 Adult experience recurrent bleed into:
→ large joints & muscles
→ joint bleeding →severe acute pain
 Repeated bleed lead to destruction:
→ cartilage
→ bone
→ muscle wasting
→ chronic pain
 Moderate hemophilia (1-5% clotting factor):
→ typically diagnosed by the age of 5 years
→ bleeding episodes occur less frequently
 Mild hemophilia (> than 5% clotting factor)
→ diagnosed later following trauma, tooth
extraction
or surgery
→ spontaneous bleeding is rare
 In 1990s, more than 80% of severe hemophilia
patients were infected with viral illnesses
→ HIV, hepatitis B & C
 In children & adolescents higher rate of anxiety
disorder have been reported in hemophilic than
asthmatics
 Physician are reluctant to prescribe opiates
→ despite the severe pain
 Individual, group and family psychotherapy
→ useful psychotherapeutic
 Caution is needed in prescribing psychotropic
→ dose of antidepressant, antipsychotic & opiate
→ reduced to compensate for hepatic impairment
→ may ↑ the risk of bleeding
 Hemophilia & AIDS patients face many stressors:
→ opportunistic infection
→ physical wasting, declining health, chronic pain
→ CNS complications…….
 Mother of HIV +ve hemophilic more distressed than
mother of HIV –ve hempphilic
 After death from AIDS, bereaved families:
→ extensive psychologic counseling & support
 Study in Japan found → 7-9 years after death
bereaved family members → deep sorrow & grief
→ regret, anger, guilt
 70% of bereaved family → restricting daily activities
 50% of bereaved family → mental heath problems
Hematologic side effects & drug
:interaction of psychotropic agents
 Antipsychotic:
→ aripiprazole & ziprasidone
→ do not have → hematologic side effects
 Agranulocytosis is rare → most common & serious
 Low potency > high potency
 Clozapine causes agrnulocytosis → 0.8 %
→ highest risk in → first 6 months → ↓ significantly
→ case fatality rate → 4.2-16%
(growth stimulating factor GSF)
→ Weekly WBC count is necessary
 If WBC count < 2000/mm
or absolute neutrophil count < 1000/mm
→ immediate cessation of clozapine
 Stopping clozapine → recovery in WBC in 3 weeks
 Mortality risk associated with agranulocytosis
→ ↑ if infection occur while still on the drug
 As Clozapine cause bone marrow suppression:
→ GSFs → normal bone marrow production
 Potential hematologic side effects:
→ aplastic anemia, neutropenia, eosinophilia
→ thrombocytopenia
 Antidepressants:
 SSRIs inhibit platelet function → bruising & bleeding
→ especially → with aspirin or NSAIDs
 SSRIs:
↑ CNS serotonin
↓ platelets serotonin → ↓ platelets aggregation
 Upper GIT bleeding may occur at a frequency from
1 in100 to 1 in 1000 patient-year exposure to high-
affinity drugs with SSRIs → elderly
 Caution is advised in patient at high risk of GI
bleeding
→ consider prescribing a antidepressant
 Patients taking SSRIs should generally use
→ smaller doses or avoid aspirin or NSAIDs
 Risk of GI bleeding
→ highest among patients on both SSRIs & NSAIDs
 While the evidence to date
→ SSRIs do not cause intracranial bleeding
→ there is a report that patients taking
→ SSRIs along with statins
→ higher risk for subarachnoid hemorrhage
 While some reviews have concluded there is
→ no ↑ risk of combining SSRIs with warfarin
→ case reports of bleeding with concomitant use
of SSRIs & warfarin
 Fluoxetine is the most commonly offending agents.
 Interactions between warfarin & SSRIs
→ potentially serious consequences
→ enhanced or reduced anticoagulant activity
 The possible mechanisms → cytochrome p450
 Fluoxetine, fluvoxamine, paroxetine
→ highest potential → interaction
 Citalopram, nefazodone, sertraline
→ relatively less likely to interact with warfarin
 Agrnulocytosis due to TCAs is a rare
 Idiosyncratic condition → bone marrow toxicity
 Lower frequency than antipsychotic
 Agrnulocytosis has been associated:
→ imipramine
→ clomipramine
→ desipramine
 Clomipramine-induced agranulocytosis
→ recombinant granulocyte colony-stimulating factor
 Benzodiazepines:
 Agrnulocytosis has rarely been reported
 No causal relationship has been established
 No relationship between daily dose or total
cumulative dose & occurrence of hematologic side
effects
 Lithium:
 Lithium stimulate leukocytosis with true proliferative
response
 In patients on lithium therapy:
documented increases in the:
→ number of platelet
→ platelet serotonin & histamine levels
 Lithium-induced hematologic side effects
→ manage hematologic toxicities associated with
other agent & disorder
 Patients with persistent leucopenia
&thrombocytopenia
following chemotherapy or radiotherapy
→ can be treated with lithium
 Anticonvulsants & mood stabilizers:
 Carbamazepine should be avoided
→ history of bone marrow depression
→ Produce a transient reduction in WBCs
→10% of patients during first 4 months
 Very rarely it causes potentially:
→ fatal agranulocytosis
→ aplastic anemia
 Baseline CBC count → advised before starting
 If the WBCs count drop below 3500/mm
→ carbamazepine should be stopped
 Carbamazepine stimulate it’s own metabolism
→ after being taken for a period of time
→ suddenly decrease
 Induce hepatic metabolism
→ reduces the anticoagulant effect of warfarin
→ Carbamazepine level & INR will need to be
monitored frequently
 Neutropenia, thrombocytopenia & macrocytic
anemia
→ have been associated with valproate
 Lamotrigine may also cause agrnulocytosis
 All anticonvulsants should be discontinued when
the WBCs count drop below 3000/mm
Think you