Week of 10–16 August 2026¶
Should patients with antiphospholipid antibody syndrome without thrombotic or obstetric complications receive aspirin for primary prophylaxis?¶
Answer: Not routinely. The evidence is weak and of low quality, so we make a case-by-case determination based on other vascular risk factors, end-organ complications, or arterial thrombosis risk factors.
- The 2019 EULAR recommendations do recommend low-dose aspirin (75–100 mg) for asymptomatic patients with a high-risk aPL profile — but this rests on a meta-analysis of seven observational studies.
- The APLASA RCT found no benefit of aspirin over placebo.
- The 2024 BSH guidance supports the case-by-case approach, favouring risk-factor modification over routine antithrombotic prophylaxis:
Recommendations
- Routine use of LDA or hydroxychloroquine for primary prevention of thrombosis in asymptomatic aPL carriers is not recommended (2B).
- We suggest that all individuals found to have persistently positive aPL with or without additional vascular risk factors receive thromboprophylaxis in high-risk situations such as following surgery or prolonged immobility (2C).
- We suggest that irrespective of the aPL profile, all individuals receive advice to improve modifiable risk factors for thrombosis (1C).
- We suggest that all asymptomatic individuals with aPL be risk assessed for cardiovascular risk factors including hypertension and hyperlipidaemia, and standard interventions including diet, lifestyle modifications and statins should be considered when these are detected (2B).
Appendix
Medium-high aPL titres. - Anticardiolipin (aCL) antibody of IgG and/or IgM isotype in serum or plasma present in titres >40 IgG phospholipid (GPL) units or >40 IgM phospholipid (MPL) units, or >the 99th percentile, measured by a standardised ELISA. Antibeta2 glycoprotein I antibody of IgG and/or IgM isotype in serum or plasma in titre >the 99th percentile, measured by a standardised ELISA.
High-risk aPL profile. - The presence (in 2 or more occasions at least 12 weeks apart) of lupus anticoagulant (measured according to ISTH guidelines), or of double (any combination of lupus anticoagulant, aCL antibodies or antibeta2 glycoprotein I antibodies) or triple (all three subtypes) aPL positivity, or the presence of persistently high aPL titres.
Low-risk aPL profile. - Isolated aCL or antibeta2 glycoprotein I antibodies at low-medium titres, particularly if transiently positive.
Related: 0011 — TPO-RAs in ITP with positive APLAs — the same aPL-driven thrombotic-risk question in a different setting.
Source: Guidelines on the investigation and management of antiphospholipid syndrome
What are the recommendations for endoscopy in patients presenting with confirmed IDA?¶
Answer: Postmenopausal women and all men with confirmed iron deficiency (ID) or IDA should undergo bidirectional endoscopy; in premenopausal women the decision is individualized.
- Postmenopausal women and men — bidirectional endoscopy, consistent with multiple other organizations (strong recommendation, moderate quality of evidence).
- Premenopausal women — the AGA still suggests bidirectional endoscopy over iron replacement alone, but this is a conditional recommendation (moderate quality of evidence):
In asymptomatic premenopausal women with iron deficiency anemia, the AGA suggests bidirectional endoscopy over iron replacement therapy only.
Comment: Patients who place a high value on avoiding the small risk of endoscopy, particularly those who are young and might have other plausible reasons for IDA, and a low value on the very small risk of missing a gastrointestinal malignancy would reasonably select an initial course of iron replacement therapy and no initial bidirectional endoscopy.
- Our approach in premenopausal women: identify and correct abnormal vaginal bleeding and re-assess at a short interval of 3–6 months. If IDA persists or other red flags are present, proceed with endoscopy.
Source: AGA Clinical Practice Guidelines on the Gastrointestinal Evaluation of Iron Deficiency Anemia
What is considered a safe threshold for neuraxial anesthesia in patients with bleeding disorders?¶
Answer: High-quality evidence is lacking. A 2025 ISTH SSC Delphi consensus proposes disorder-specific hemostatic thresholds; in general, risk is higher for epidural than spinal anesthesia, and the bleeding history and platelet-count stability influence the safe threshold.
Spinal/epidural hematomas likely occur in between 1:10 000 and 1:200 000 procedures. Risk is believed to be greater in patients with bleeding disorders/thrombocytopenia, and there are no existing comprehensive recommendations to guide neuraxial anesthesia in these patients.
Generally acceptable thresholds by disorder:
| Disorder | Generally acceptable threshold |
|---|---|
| ITP | Platelets >70 ×10⁹/L |
| Gestational thrombocytopenia | Platelets >70 ×10⁹/L |
| Thrombocytopenia in hypertensive disorders of pregnancy (preeclampsia with severe features, eclampsia, HELLP) | Case-by-case with a multidisciplinary team. In HELLP, also check INR, APTT, and fibrinogen; platelets ≥70 ×10⁹/L is generally acceptable when there is no hepatic coagulopathy (normal INR/APTT/fibrinogen). |
| VWD (any subtype) | FVIII activity ≥50 IU/dL and VWF activity ≥50 IU/dL for a mild bleeding history; with a severe bleeding history, the same thresholds after treatment. Type 2B with severe bleeding: case-by-case. |
| Inherited platelet function disorders (IPFDs) | Mild IPFD + mild bleeding: consider 60–90 min after desmopressin ± tranexamic acid if treatment-responsive. Bleeding despite prior treatment is a relative contraindication. Severe IPFDs (Bernard–Soulier syndrome, Glanzmann thrombasthenia) are relatively contraindicated. |
| FVII deficiency | FVII >50% |
| Hemophilia A/B and symptomatic carriers | FVIII/FIX ≥50 IU/dL (mild bleeding history); ≥80 IU/dL (severe bleeding history) |
| FXI deficiency | FXI >50% |
| FXIII deficiency | ≥50 IU/dL (mild bleeding history); ≥80 IU/dL for spinal (severe bleeding history) |
| Hypo-/dysfibrinogenemia (Clauss method) | Mild bleeding: ≥2.0 g/L for epidural insertion, ≥1.5 g/L for spinal or epidural removal. Severe bleeding: ≥2.0 g/L for spinal, or epidural insertion/removal. |
What are the mechanisms of acquired von Willebrand syndrome?¶
Answer: Multiple mechanisms, none very well understood. Unlike acquired hemophilia A (AHA), acquired von Willebrand syndrome (AvWS) occurs most of the time with an underlying disorder, and some disorders act through overlapping mechanisms.
Increased plasma clearance of VWF — the main route:
- Antibodies — MGUS, multiple myeloma, SLE: anti-VWF antibodies form immune complexes that are cleared by the reticuloendothelial system (RES).
- Adsorption onto cell surfaces — high-molecular-weight (HMW) multimers bind cells and are then cleared:
- tumor cells in lymphoproliferative disease and solid cancers; in MGUS, aberrant GPIb expression on abnormal plasma cells drives selective binding;
- platelets in essential thrombocythemia and other myeloproliferative neoplasms (MPNs) — the platelet count is inversely related to the plasma HMW-multimer defect.
- Shear stress — LVADs and valvular disease: HMW multimers sheared by mechanical stress and by ADAMTS13-mediated proteolysis.
- Increased proteolysis — MPNs may also lower VWF through increased plasma proteolysis.
Decreased synthesis — hypothyroidism.
An illustrative case: lymphoma-associated AvWS responsive to splenectomy — the likely mechanism was VWF antibody-mediated inhibition and/or VWF adsorption onto platelets sequestered in the spleen or onto the massive number of tumor cells.
Source: Acquired von Willebrand syndrome: focused for hematologists
How does congenital dysfibrinogenemia present in women?¶
Answer: In women, congenital dysfibrinogenemia presents mainly as heavy menstrual bleeding and obstetric complications — postpartum hemorrhage (PPH) and miscarriage — at rates well above the general population.
From a Prospective Rare Bleeding Disorders Database cohort of 59 women with congenital fibrinogen disorders (32 had 70 pregnancies):
- Heavy menstrual bleeding — 36% in dysfibrinogenemia and 27% in hypofibrinogenemia, vs 75% in afibrinogenemia.
- Postpartum hemorrhage — 36% overall, far above the general-population 1–10%; similar in dysfibrinogenemia (35%) and hypofibrinogenemia (36%).
- Miscarriage — 23% overall, above the general-population 10–20%; dysfibrinogenemia 37%, hypofibrinogenemia 31%. Occurred even in 50% of otherwise-asymptomatic dysfibrinogenemic women.
- Bleeding during pregnancy was uncommon — 2/70 pregnancies (4%), both dysfibrinogenemic.
- No difference in miscarriage or PPH between dysfibrinogenemic women with vs without hotspot variants (P = .94).
A case report of one woman across successive pregnancies underscores that presentation is heterogeneous and prior obstetric history and genotype do not reliably predict future complications — complications occurred despite normal ROTEM (FIBTEM). Management is expert-opinion–based and individualized.
What is the influence of race and ethnicity on the diagnosis of VWD?¶
Answer: Race and ethnicity bias VWD diagnosis in both directions — overdiagnosis from an assay artifact, and underdiagnosis from higher baseline VWF levels.
- Overdiagnosis — the D1472H polymorphism is common in Black patients (~2 of 3, vs ~1 of 6 White patients) and lowers measured VWF ristocetin cofactor activity (VWF:RCo), which can be misread as type 2M VWD. The seminal Blood study traced this to exon 28 polymorphisms that affect the ristocetin-based assay:
The diagnosis of von Willebrand disease relies on abnormalities in specific tests of von Willebrand factor (VWF), including VWF antigen (VWF:Ag) and VWF ristocetin cofactor activity (VWF:RCo). When examining healthy controls enrolled in the T. S. Zimmerman Program for the Molecular and Clinical Biology of von Willebrand disease, we, like others, found a lower mean VWF:RCo compared with VWF:Ag in African American controls and therefore sought a genetic cause for these differences. For the African American controls, the presence of 3 exon 28 single nucleotide polymorphisms (SNPs), I1380V, N1435S, and D1472H, was associated with a significantly lower VWF:RCo/VWF:Ag ratio, whereas the presence of D1472H alone was associated with a decreased ratio in both African American and Caucasian controls. Multivariate analysis comparing race, SNP status, and VWF:RCo/VWF:Ag ratio confirmed that only the presence of D1472H was significant. No difference was seen in VWF binding to collagen, regardless of SNP status. Similarly, no difference in activity was seen using a GPIb complex-binding assay that is independent of ristocetin. Because the VWF:RCo assay depends on ristocetin binding to VWF, mutations (and polymorphisms) in VWF may affect the measurement of "VWF activity" by this assay and may not reflect a functional defect or true hemorrhagic risk.
- Underdiagnosis — Black patients have higher average VWF:Ag (Black vs White women) and higher VWF and FVIII levels (African American adults vs other races), so genuine VWD can be missed against population-general reference ranges.
For broader population-level context, see Montgomery & Flood, What have we learned from large population studies of von Willebrand disease?.
Source: Laboratory-based inequity in thrombosis and hemostasis: review of the evidence