Keywords
thrombocytopenia - platelet dysfunction - anticoagulation - thrombotic risk - bleeding
risk
Introduction
Platelet disorders (PDs) comprise acute and chronic conditions resulting from reduced
platelet count and/or impaired platelet function. Typical bleeding symptoms include
petechiae, ecchymoses, prolonged bleeding after injury, epistaxis, or menorrhagia.
Bleeding severity ranges from almost trivial to very severe.[1]
[2]
[3]
Patients with PDs can coincidently acquire transient or permanent prothrombotic conditions,
which necessitate prophylactic or therapeutic anticoagulation. Prophylactic anticoagulation
is usually administered in hospitalized medical patients, after surgery, or in outpatients
at increased risk of thrombosis (e.g., some cancer patients).[4]
[5]
[6] Therapeutic anticoagulation is indicated to treat and prevent venous thromboembolism
(VTE),[7]
[8] to prevent stroke in patients with atrial fibrillation (AF),[9]
[10] and to reduce the risk of thromboembolism in patients with mechanical heart valves.[11]
[12]
Anticoagulation in PD patients is a matter of great concern because it increases the
risk of bleeding. This could add to the hemorrhagic risk related to the platelet defect.
Therefore, each decision to provide anticoagulation must be balanced by tailoring
bleeding and thrombotic risks at an individual level. In this review, we provide a
summary of how to approach patients with PD who have an indication for anticoagulation.
Platelet Disorders
Thrombocytopenia
Thrombocytopenia is defined as reduced blood platelets less than 150 × 109/L.[13] For intensive care patients[14] and for patients with immune thrombocytopenia,[15] thrombocytopenia is defined as platelets less than 100 × 109/L, as bleeding symptoms unlikely occur if platelet counts are above this threshold.
Platelet counts less than 50 × 109/L is further specified as severe thrombocytopenia.[16] Confirmed thrombocytopenia results from (1) increased platelet consumption (e.g.,
immune-mediated platelet destruction, bleeding, disseminated intravascular coagulation
[DIC]); (2) decreased platelet production (e.g., bone marrow failure, myelodysplasia,
and chemotherapy); and (3) increased sequestration of platelets (e.g., due to splenomegaly).
A standardized workup is required to diagnose primary thrombocytopenia, or secondary
thrombocytopenias due to an underlying disease.[17]
Platelet Dysfunction
Acquired platelet function defects (PFDs) mainly occur due to drug therapies and/or
complicating systemic disease.[18] Antiplatelet agents, nonsteroidal anti-inflammatory drugs, β-lactam antibiotics,
anticonvulsants, antidepressants, and angiotensin 2 inhibitors impair platelet function.[19] Alcohol, flavonoids-rich foods (e.g., red wine, cocoa, and green tea), spices (e.g.,
cumin), or herbal products (e.g., ginkgo biloba, garlic) also reduce platelet function.[20]
[21]
[22]
[23]
[24] Myelodysplastic and myeloproliferative syndromes, diseases with paraproteinemia,
liver and/or renal failure, and severe trauma are associated with platelet dysfunction
and/or additional thrombocytopenia.[25]
[26]
[27] Moreover, ventricular assist devices and extracorporeal circulations frequently
cause PFDs in addition to other hemostasis defects such as acquired von Willebrand
syndrome.[28] Of note, platelet hyperactivity can also occur increasing the risk of thrombosis
(e.g., in patients with myeloproliferative neoplasms).[29] PFDs are diagnosed by means of platelet function tests.[30]
Inherited PDs represent a peculiar group of rare conditions involving only platelets
or presenting as syndromes with additional clinical manifestations.[1]
[31] For instance, patients with MYH9-related thrombocytopenia—the most frequent inherited PD—may develop sensorineural
deafness, nephropathy, juvenile cataracts, and chronic elevation of liver enzymes.[32] Inherited PD can present with thrombocytopenia, alterations of platelet size, platelet
dysfunction, or as a combination of these findings.[1]
[33] Inherited PDs featured by platelet dysfunction such as Bernard–Soulier syndrome
or Glanzmann thrombasthenia have more severe bleeding symptoms than those with thrombocytopenia
only.[1]
[34] Diagnostic tools involve clinical evaluation, immune-morphologic assessment on blood
smears, platelet function assays, and genetic testing.[1]
[2]
[35]
[36]
Treatment of Platelet Disorders
Therapeutic goals include the treatment of underlying diseases, prophylaxis, and management
of bleeding episodes. Avoidance of drugs impairing platelet function or contact sports,
providing regular dental cares, and hormonal therapy to reduce menorrhagia in women
of childbearing age can reduce bleeding episodes. If sideropenic anemia is present,
iron should be substituted. Pharmacological treatment of bleedings mainly rely on
tranexamic acid and desmopressin.[1]
[37]
[38] In certain acquired (e.g., immune thrombocytopenia) and inherited PD, thrombopoietin-receptor
agonists can transiently increase platelet counts and facilitate invasive procedures.[39]
[40]
[41] Against more severe bleeding, platelet transfusions and/or recombinant-activated
factor VII can be applied.[42] Importantly, platelet concentrates should be avoided whenever possible in Glanzmann
thrombasthenia or Bernard–Soulier syndrome to reduce the risk for isoantibody formation
against the glycoproteins absent on patients' and expressed on blood donors' platelets,
which render further platelet transfusions ineffective.[43]
Bleeding Risk Assessment
Various bleeding assessment tools (BATs) based on history-taking questionnaires have
been created to assess the bleeding tendency, guide treatment, and predict future
bleedings in patients with different hemorrhagic diatheses.[44] Two frequently used BATs for PD are the World Health Organization (WHO)[45] and the International Society of Thrombosis and Haemostasis (ISTH) BAT.[34]
[46] The WHO scale is a global, nonstructured tool that categorizes bleeding into four
groups: grade 0, no bleeding; grade 1, petechiae; grade 2, mild blood loss; grade
3, gross blood loss; and grade 4, debilitating blood loss. The ISTH-BAT sums 14 distinct
scores corresponding to specific graduated bleeding manifestations ([Supplementary Table S1] [online only]).
Recent studies on patients with inherited PD showed that the degree of basal bleeding
symptoms predicts the risk of spontaneous and provoked future bleedings.[34] Particularly, a substantial bleeding history (WHO grade ≥ 2 or ISTH-BAT score ≥ 6),
female sex, and certain procedures (i.e., cardiovascular or urological interventions)
predict a higher risk of surgery-related hemorrhagic complications.[39] Women with PD have a higher risk of postpartum hemorrhage when a history of maternal
bleeding and/or platelet count lower than 50 × 109/L is present.[47]
[48]
Both BATs have not been evaluated for acquired PD. However, even these subjects—particularly
those with persisting symptoms—are likely at higher bleeding risk when having a WHO
bleeding scale of ≥2 or an ISTH-BAT total score of ≥6. Sometimes, their primary diseases
carry additional hemorrhagic risks due to a compromised plasmatic coagulation (e.g.,
due to chronic liver disease).[49] We therefore recommend investigating platelet function and plasmatic coagulation to judge the risks and benefits of anticoagulation in patients
with PD.
Thrombotic Risk Assessment
Thrombotic Risk Assessment
Thrombotic risk assessment varies with clinical settings. The Caprini score assesses the risk of surgery-associated VTE. In the general population not
undergoing thromboprophylaxis, the incidence rates of thrombotic events correlated
with this model were <0.5, 3, ≥5, and ≥6% when the scores were 0, 1 to 2, ≥ 3, and ≥ 5,
respectively.[4]
[50]
[51]
The American College of Chest Physicians (ACCP) classified three surgical categories
with a VTE risk: <10% (minor surgery), 10 to 40% (moderate-risk surgery), and up to
80% for high-risk procedures (e.g., knee or hip arthroplasty).[52]
The Khorana score assesses the VTE risk for ambulatory and hospitalized cancer patients including
clinical and laboratory criteria: type of neoplasia (pancreatic and stomach cancer
account for the highest risk), prechemotherapy platelet and leukocyte count, hemoglobin
concentration, use of red cell growth factors, and body mass index. Scores ≥2 qualify
patients worthy of prophylactic anticoagulation.[53]
The Padua score is a well-known model to identify medical patients at high risk of VTE (score > 4)
and guide prophylactic anticoagulation. This score includes a previous history of
VTE, immobilization, the presence of thrombophilia, active cancer, recent trauma or
surgery, elderly, heart or respiratory failure, acute infarction or stroke, acute
infection or rheumatologic disorder, ongoing hormonal treatments, and obesity.[54]
Regarding therapeutic anticoagulation, the CHA2DS2-VASc score was established to stratify patients with AF according to their risk of
stroke or other arterial thromboembolism (2 points for previous embolic event and
age ≥75 years; 1 point each for congestive heart failure, hypertension, diabetes mellitus,
age 65–74 years, vascular disease, and female sex).[55] Patients with scores ≥2 should start anticoagulation if no high bleeding risk is
present.
Patients with acute VTE and implanted mechanical heart valve prosthesis have a high
risk of thrombosis and stringently require therapeutic anticoagulation.[5]
[7]
[8] However, the risk of recurrence after an acute VTE event is considered to be highest
during the first 30 days after the VTE has occurred,[56]
[57] being the minimum time where therapeutic anticoagulation is mandatory.[58] For mechanical heart valves, the kind and position of the valve play a role. Mechanical
mitral valves or replacement of multiple valves bear the highest thromboembolic risk,
whereas the risk is lower for aortic valves.[59] Moreover, biological valves have a much lower thrombotic risk and do not necessitate
long-term anticoagulation.[11] Some systemic disorders necessitate therapeutic anticoagulation such as the antiphospholipid
syndrome,[60] DIC,[61] or heparin-induced thrombocytopenia,[62] even if platelet counts are very low. Finally, treatments to prevent bleeding such
as recombinant factor VIIa or platelet transfusions may increase the venous and arterial
thrombotic risk.[3]
[63]
While none of the described stratification tools have been validated to assess the
risk of thrombosis in patients with PD, they provide a solid basis to identify subjects
with an increased thromboembolic risk. Therefore, we include them into a benefit–risk
assessment for PD patients to decide if anticoagulation is indicated.
Alternatives to Anticoagulation
Alternatives to Anticoagulation
Despite significantly less effective than prophylactic anticoagulation, mechanical
prophylaxis is indicated for PD patients with very high bleeding risk.[64] Here, intermittent pneumatic compression is more effective than elastic compressive
stockings.[65] However, patients who can receive pharmacoprophylaxis do not benefit from adjunctive
mechanical prophylaxis.[66]
Patients with acute VTE not tolerating therapeutic anticoagulation may receive an
inferior vena cava filter. Because of possible complications of this approach, the
indication should be evaluated individually.[67]
Thromboprophylaxis
Thrombocytopenia
Most guidelines on thromboprophylaxis rely on studies that excluded patients with
platelets less than 50 × 109/L. However, above this threshold, prophylactic anticoagulation appears safe if no
other hemorrhagic risk factors are present.[68] For oncology patients with platelet counts between 25 and 50 × 109/L, the ISTH suggests prophylactic anticoagulation after acute thrombotic episodes
with low risk of progression or subacute or chronic thrombosis.[58] Patients with platelets below 25 × 109/L require an individual decision weighing thrombotic and bleedings risks.
The anticoagulant of choice depends on the clinical setting. A meta-analysis of 20
studies including approximately 10,000 cancer patients undergoing surgery revealed
no difference between perioperative thromboprophylaxis with low-molecular-weight heparin
(LMWH) and unfractionated heparin (UFH), and LMWH compared with fondaparinux on mortality,
thromboembolic outcomes, and bleeding. A lower incidence of wound hematoma occurred
with LMWH compared with UFH.[69] Direct oral anticoagulants (DOACs) apixaban and rivaroxaban may serve as alternatives
for LMWH for thromboprophylaxis in ambulatory patients starting chemotherapy, including
those with mild thrombocytopenia.[70]
[71] Here, a high risk of gastrointestinal or urogenital bleeding should be excluded.[72] Eventually, a randomized study with more than 3,000 intensive care patients including
those with mild thrombocytopenia revealed a better safety profile of LMWH over UFH.[73]
Platelet Dysfunction
So far, only one study has systematically explored the risk of VTE in patients with
PD undergoing surgery.[74] Out of more than 200 procedures performed in 133 subjects affected by 22 inherited
PDs, the risk of postsurgical VTE was lower than in the general population but not
negligible, and correlated with the Caprini score and the ACCP procedure-related risk stratification. Both mechanical and pharmacologic
prophylaxis reduced the occurrence of VTE. Most of the anticoagulated patients received
enoxaparin at a median daily dosage of 4,000 IU (interquartile range [IQR]: 2,000–5,000)
starting from the day of surgery for a median duration of 15 days (IQR: 7–18). Of
note, the rate of postsurgical bleedings did not significantly differ between anticoagulated
and non-anticoagulated patients. The study also showed that patients with substantial
platelet dysfunction were not exempt from postsurgical VTE. In fact, two patients
affected with Glanzmann thrombasthenia and biallelic Bernard–Soulier syndrome developed
postprocedural VTE. Despite a high individual VTE risk (Caprini scores of 8 and 12, respectively), both subjects did not receive anticoagulation,
presumably because of the perceived high bleeding risk. Selleng et al. also reported
on a patient with MYH9-related thrombocytopenia not receiving prophylactic anticoagulation who developed
postsurgical VTE.[75] These cases show that postsurgical thromboprophylaxis should not be withhold in
inherited PD patients, when prothrombotic risk factors are present. This concept is
reasonably transferrable to persistent acquired PD.
Therapeutic Anticoagulation
Therapeutic Anticoagulation
Thrombocytopenia
For thrombocytopenia and cancer-associated acute VTE, the ISTH suggests full-dose
anticoagulation at platelet counts greater than 50 × 109/L, and to consider an adapted regimen if platelets fall below that level. This includes
platelet transfusion support to maintain platelet counts at 40 to 50 × 109/L, if patients have high-risk features of cancer-associated VTE such as symptomatic
segmental or proximal pulmonary embolism, proximal deep vein thromboses, or a history
of recurrent/progressive thrombosis. Lower risk thromboses such as distal deep vein
thromboses, incidental subsegmental pulmonary embolism, and catheter-related thromboses
may be anticoagulated with half therapeutic doses. Prophylactic-dose LMWH may be considered
for patients with platelets of 25 to 50 × 109/L. Anticoagulation is stopped for patients with platelets less than 25 × 109/L, although prophylactic dosage might be reasonable as long as platelet counts exceed
10 × 109/L.[58] The minimum treatment duration should cover 6 months or longer, if the tumor persists
and the VTE risk remains high.[76]
Thrombocytopenia is also common in AF patients with greater than 10% being affected.[77] AF guidelines acknowledge low platelet counts as a risk factor for bleeding,[9] but do not recommend specific platelet thresholds to adjust or withhold anticoagulation.
However, AF patients with mild or moderate thrombocytopenia may safely be anticoagulated
and DOACs may be as safe and effective as in non thrombocytopenic patients. A cohort
study including 367 patients with thrombocytopenia (platelets <100 × 109/L) found that DOAC therapy (n = 181) was associated with a lower tendency for major bleeding with no significant
difference in ischemic stroke/systemic embolism or death when compared with warfarin
(n = 186).[78] A retrospective study compared AF patients treated with either warfarin (n = 6,287) or DOACs (n = 5,240). DOAC patients with reduced platelet counts (<150 × 109/L) had significantly lower mortality rates during a median follow-up of 40.6 months
compared with warfarin controls.[79] Caro and Navada reported one patient with more severe thrombocytopenia associated
with myelodysplastic syndrome and two with acute myeloid leukemia and AF, who did
not develop major bleeding despite anticoagulation (1 rivaroxaban, 2 warfarin) during
an average follow-up of 203 days.[80]
A proof-of-concept study revealed that AF patients with mild thrombocytopenia might
benefit from DOACs at reduced doses. Sixty-two patients with AF and platelet counts
from 50 to 100 × 109/L were treated with rivaroxaban 15 mg once daily (33.9%), dabigatran 110 mg twice
daily (54.8%), or apixaban 2.5 mg twice daily (11.3%) and compared with matched AF
subjects with normal platelet counts being treated with the recommended doses of DOACs.
Thrombocytopenic patients had similar rates of major bleeding (1.8 vs. 2.7%/year,
p = 0.49), clinically relevant non-major bleeding (1.5 vs. 1.1%/year, p = 0.74), ischemic stroke and transient ischemic attacks (1.8 vs. 1.5%/year, p = 0.8), and death (1.06 vs. 1.11%/year, p = 0.96). The risk of bleeding and stroke was unaffected by the type of DOAC.[81]
Finally, cancer patients on chemotherapy with newly diagnosed AF are suggested to
take a DOAC over vitamin K antagonist or LMWH, if no contraindications (e.g., gastrointestinal
cancers) are present and no relevant drug-to-drug interactions are expected.[82] We therefore conclude that AF patients with platelets greater than 50 × 109/L should receive therapeutic anticoagulation, preferably with DOACs. For patients
with lower platelet counts, reduced dose regimens may be appropriate to reduce the
bleeding risk based on an individual benefit–risk evaluation. An individual management
is also necessary for patients with mechanical heart valves or other high-risk situations,
who develop thrombocytopenia.
Platelet Dysfunction
Anticoagulation in inherited PD was reported for patients with Glanzmann thrombasthenia,[74]
[83]
[84]
[85]
[86]
[87]
[88] Bernard–Soulier syndrome[74] and MYH9-related thrombocytopenia[75]
[89] who developed VTE. The thrombotic manifestations were often provoked by a transient
risk factor such as surgery or a central venous catheter, which highlights the relevance
of thromboprophylaxis. In acute VTE, therapeutic dose anticoagulation with UFH or
LMWH was administered at most. None of the reported patients received DOACs as first
choice. Long-term anticoagulation was mainly performed with vitamin K antagonists
or LMWH, and anticoagulation-related bleeding was rare. In the SPATA-DVT study, a
patient with Glanzmann thrombasthenia and deep vein thrombosis received therapeutic
dose enoxaparin for 3 months without bleeding complications.[74] Only one severe hemorrhagic episode due to gastrointestinal angiodysplasia was reported
in a Glanzmann thrombasthenia patient receiving anticoagulation with rivaroxaban.
This patient had a severe bleeding phenotype even before anticoagulation, which had
likely aggravated but not caused the hemorrhage.[85]
Thus, a limited course of anticoagulation appears feasible in patients with PD without
a dramatic increase of the bleeding risk. However, long-term anticoagulation might
overproportionally increase the bleeding risk. We therefore propose to administer
therapeutic anticoagulation during the first month after an acute VTE. Further course
of treatment should consider the type of thrombosis, the bleeding tendency of each
patient, the treatment effectiveness, and the individual risk of VTE recurrence to
adapt the anticoagulation regimen. The indication for anticoagulation in AF patients
should be based on the CHA2DS2-VASc score and treatment should be managed similar to patients with thrombocytopenia.
Reduced doses of LMWH or DOACs may be appropriate for long-term anticoagulation, if
intolerable bleeding symptoms occur during therapeutic dose anticoagulation.
Few reports deal with patients receiving prosthetic heart valves, mainly addressing
their perioperative management. Garcia-Villarreal et al described a Glanzmann thrombasthenia
patient undergoing prosthetic mitral valve replacement who developed severe bleeding
complications during postsurgery anticoagulation including severe hematuria and gastrointestinal
bleeds.[90] Only the shift to a biologic valve prosthesis could control the situation as anticoagulation
could be stopped afterward. This case illustrates the relevance to accurately plan
such procedures and to ascertain whether less thrombogenic cardiac or arterial devices
can be implanted to avoid long-term anticoagulation after the procedure. In addition,
acquired von Willebrand syndrome can occur in patients with prosthetic heart valves
and complicate postprocedural bleedings.[91]
Conclusions
There is clear evidence that patients with PD can develop thrombosis in the presence
of prothrombotic risk factors despite their bleeding phenotype. Moreover, the additional
risk of bleeding resulting from prophylactic anticoagulation is substantially lower
compared with the risk of bleeding during longer-term therapeutic dose anticoagulation
whenever a VTE has developed. As a consequence, prophylactic anticoagulation should
be considered if the thrombotic risk is high.
In [Table 1], we propose how to guide perioperative thromboprophylaxis in patients with PD according
to the Caprini score. Briefly, we suggest mechanical prophylaxis when the thrombotic risk is only
low or intermediate, and prophylactic anticoagulation with LMWH when the VTE risk
is high. In case of postsurgical excessive bleeding, LMWH should be postponed until
effective hemostasis has been achieved. These principals can be applied likewise for
other medical conditions with an increased thrombotic risk adapting the described
tools for risk stratification.
Table 1
Approach to postsurgical VTE prophylaxis in patients with inherited and persistent
acquired platelet disorders
|
VTE risk assessment
|
Advisable postsurgical VTE prophylaxis
|
Adjustment in case of postsurgical excessive bleeding
|
|
Low (Caprini score: 0–2)
|
Mechanical prophylaxis[a]
|
–
|
|
Moderate
(Caprini score: 3–4)
|
Mechanical prophylaxis[a]
Consider pharmacologic prophylaxis[b] in case of expected prolonged immobilization and low individual bleeding risk[c]
|
Start mechanical prophylaxis[a] and consider to switch to pharmacologic one[b] as soon as bleeding has been stopped and adequate hemostatic balance has been restored
|
|
High/very high
(Caprini score: ≥ 5)
|
Pharmacologic prophylaxis[b]
|
Start mechanical prophylaxis[a] and switch to the pharmacologic one[b] as soon as bleeding has been stopped and adequate hemostatic balance has been restored
|
Abbreviation: BAT, bleeding assessment tool; ISTH, International Society of Thrombosis
and Haemostasis; LMWH, low-molecular-weight heparin; WHO, World Health Organization;
VTE, venous thromboembolism.
a Pneumatic compression (preferably) or compression stockings should be started immediately
after surgery and continued for 2 weeks.
b LMWH at a prophylactic dosage, to be started within 6 hours after surgery and continued
for 2 weeks.
c WHO bleeding scale < 2 or ISTH-BAT < 6.
Therapeutic dose anticoagulation may be feasible for a defined duration without an
inacceptable high bleeding risk. However, dose reductions or withhold of anticoagulation
should be considered as soon as the VTE risk declines and if bleeding symptoms worsen.
[Table 2] summarizes considerations for therapeutic anticoagulation in PD patients and lists
potential treatment options.
Table 2
Approach to adapt therapeutic anticoagulation in patients with inherited and persistent
acquired platelet disorders
|
Bleeding risk
|
Thrombotic risk
|
Indication for anticoagulation
|
Considerations for anticoagulation
|
|
High[a]
|
High
|
Venous thromboembolism < 3 mo
Atrial fibrillation (CHA2DS2-VASc score ≥ 2)
Heart valve prosthesis (mechanical valves, multiple valve prosthesis)
|
Consider short-acting intravenous or oral drugs (UFH, DOACs), with dose reduction
after the first month if the VTE has resolved
Weigh bleeding against thrombotic risk and consider short-acting oral drugs (DOACs)
with close monitoring of bleeding symptoms
Whenever possible, consider biologic prosthesis before implantation. If a mechanical
valve has been implanted and bleeding in a patient undergoing anticoagulation cannot
be managed otherwise, switch to biologic valve
|
|
High[a]
|
Low
|
Venous thromboembolism > 3 mo
Atrial fibrillation (CHA2DS2-VASc score < 2)
Heart valve prosthesis (biologic prosthesis)
|
Consider to stop therapeutic dose anticoagulation
Consider not to start anticoagulation
Consider not to provide long-term anticoagulation
|
|
Low[b]
|
High
|
Venous thromboembolism < 3 mo
Atrial fibrillation (CHA2DS2-VASc score ≥ 2)
Heart valve prosthesis (mechanical valves, multiple valve prosthesis)
|
Consider a usual course of anticoagulation and plan a reevaluation of thrombotic risk
after 3 mo
Consider usual course of anticoagulation with periodic evaluation of bleeding symptoms
Consider usual course of anticoagulation with periodic evaluation of bleeding symptoms
|
|
Low[b]
|
Low
|
Venous thromboembolism > 3 mo
Atrial fibrillation (CHA2DS2-VASc score < 2)
Heart valve prosthesis (biologic prosthesis)
|
Consider to stop therapeutic dose anticoagulation
Consider not to start anticoagulation
Consider to stop postinterventional anticoagulation early
|
Abbreviations: BAT, bleeding assessment tool; DOACs, direct oral anticoagulants; ISTH,
International Society of Thrombosis and Haemostasis; LMWH, low-molecular-weight heparin;
UFH, unfractionated heparin; WHO, World Health Organization; VTE, venous thromboembolism.
a WHO BS ≥2 or ISTH-BAT total score ≥6 or platelet counts < 50 × 109/L.
b WHO BS <2 or ISTH-BAT total score <6 or platelet counts > 50 × 109/L.
Although most experience exists with LMWH, the advantages of DOACs may indicate this
treatment in specific situations such as AF or VTE.
Due to the scanty evidence, caution is mandatory for treatment decisions and physicians
should carefully assess and document bleeding events and thrombosis risks before and
during anticoagulation on a regular schedule to optimize individual therapy. A close
follow-up is highly recommended to provide the safest and most efficient anticoagulation
in patients with PD.
